X-53382539-G-A

Variant names:

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_ModerateBP6BP7BS2

The NM_006306.4(SMC1A):c.3252C>T(p.Ile1084Ile) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000331 in 1,209,182 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 2 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

Frequency

Genomes: 𝑓 0.0000089 ( 0 hom., 0 hem., cov: 22)

Exomes 𝑓: 0.0000027 ( 0 hom. 2 hem. )

Consequence

SMC1A
NM_006306.4 synonymous

Scores

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1B:1

Conservation

PhyloP100: 3.52

Publications

0 publications found

Variant links:

Genes affected

SMC1A (HGNC:11111): (structural maintenance of chromosomes 1A) Proper cohesion of sister chromatids is a prerequisite for the correct segregation of chromosomes during cell division. The cohesin multiprotein complex is required for sister chromatid cohesion. This complex is composed partly of two structural maintenance of chromosomes (SMC) proteins, SMC3 and either SMC1B or the protein encoded by this gene. Most of the cohesin complexes dissociate from the chromosomes before mitosis, although those complexes at the kinetochore remain. Therefore, the encoded protein is thought to be an important part of functional kinetochores. In addition, this protein interacts with BRCA1 and is phosphorylated by ATM, indicating a potential role for this protein in DNA repair. This gene, which belongs to the SMC gene family, is located in an area of the X-chromosome that escapes X inactivation. Mutations in this gene result in Cornelia de Lange syndrome. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Jul 2013]

SMC1A Gene-Disease associations (from GenCC):

Cornelia de Lange syndrome 2
Inheritance: XL Classification: DEFINITIVE, STRONG Submitted by: G2P, Labcorp Genetics (formerly Invitae)
developmental and epileptic encephalopathy, 85, with or without midline brain defects
Inheritance: XL Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), G2P
X-linked complex neurodevelopmental disorder
Inheritance: XL Classification: DEFINITIVE Submitted by: ClinGen
atypical Rett syndrome
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
Cornelia de Lange syndrome
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

SMC1A links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -8 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.45).

BP6

Variant X-53382539-G-A is Benign according to our data. Variant chrX-53382539-G-A is described in CliVar as Conflicting_classifications_of_pathogenicity. Clinvar id is 159955. Variant chrX-53382539-G-A is described in CliVar as Conflicting_classifications_of_pathogenicity. Clinvar id is 159955. Variant chrX-53382539-G-A is described in CliVar as Conflicting_classifications_of_pathogenicity. Clinvar id is 159955. Variant chrX-53382539-G-A is described in CliVar as Conflicting_classifications_of_pathogenicity. Clinvar id is 159955. Variant chrX-53382539-G-A is described in CliVar as Conflicting_classifications_of_pathogenicity. Clinvar id is 159955. Variant chrX-53382539-G-A is described in CliVar as Conflicting_classifications_of_pathogenicity. Clinvar id is 159955. Variant chrX-53382539-G-A is described in CliVar as Conflicting_classifications_of_pathogenicity. Clinvar id is 159955. Variant chrX-53382539-G-A is described in CliVar as Conflicting_classifications_of_pathogenicity. Clinvar id is 159955. Variant chrX-53382539-G-A is described in CliVar as Conflicting_classifications_of_pathogenicity. Clinvar id is 159955.

BP7

Synonymous conserved (PhyloP=3.52 with no splicing effect.

BS2

High Hemizygotes in GnomAdExome4 at 2 AD,XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SMC1A	NM_006306.4 link	c.3252C>T	p.Ile1084Ile	synonymous_variant	Exon 21 of 25	ENST00000322213.9	NP_006297.2	Q14683A0A384MR33Q68EN4
SMC1A	NM_001281463.1 link	c.3186C>T	p.Ile1062Ile	synonymous_variant	Exon 22 of 26		NP_001268392.1	G8JLG1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SMC1A	ENST00000322213.9 link	c.3252C>T	p.Ile1084Ile	synonymous_variant	Exon 21 of 25	1	NM_006306.4	ENSP00000323421.3		Q14683

Frequencies

GnomAD3 genomes

AF:

0.00000894

AC:

AN:

111832

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000188

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.00000556

AC:

AN:

179955

AF XY:

0.0000155

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000273

AC:

AN:

1097350

Hom.:

Cov.:

AF XY:

0.00000551

AC XY:

AN XY:

362750

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

26396

American (AMR)

AF:

0.00

AC:

AN:

35124

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

19373

East Asian (EAS)

AF:

0.00

AC:

AN:

30185

South Asian (SAS)

AF:

0.0000185

AC:

AN:

53928

European-Finnish (FIN)

AF:

0.00

AC:

AN:

40474

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4134

European-Non Finnish (NFE)

AF:

0.00000238

AC:

AN:

841657

Other (OTH)

AF:

0.00

AC:

AN:

46079

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00000894

AC:

AN:

111832

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

33980

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

30763

American (AMR)

AF:

0.00

AC:

AN:

10575

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2647

East Asian (EAS)

AF:

0.00

AC:

AN:

3551

South Asian (SAS)

AF:

0.00

AC:

AN:

2677

European-Finnish (FIN)

AF:

0.00

AC:

AN:

6059

Middle Eastern (MID)

AF:

0.00

AC:

AN:

239

European-Non Finnish (NFE)

AF:

0.0000188

AC:

AN:

53131

Other (OTH)

AF:

0.00

AC:

AN:

1503

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.575

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000378

ClinVar

Significance: Conflicting classifications of pathogenicity

Submissions summary: Uncertain:1Benign:1

Revision: criteria provided, conflicting classifications

LINK: link

Submissions by phenotype

Congenital muscular hypertrophy-cerebral syndrome

Uncertain:1Benign:1

Jun 04, 2024

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Feb 08, 2013

Genetic Services Laboratory, University of Chicago

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.45

CADD

Benign

(source)

DANN

Benign

0.78

PhyloP100

3.5

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over