rs73210414

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBP6_Very_Strong

The NM_006306.4(SMC1A):c.2973+45G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.013 ( 10 hom., 408 hem., cov: 20)

Exomes 𝑓: 0.028 ( 616 hom. 3821 hem. )

Failed GnomAD Quality Control

Consequence

SMC1A
NM_006306.4 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -1.20

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: Labcorp Genetics (formerly Invitae), G2P, PanelApp Australia
developmental and epileptic encephalopathy, 85, with or without midline brain defects
Inheritance: XL Classification: DEFINITIVE, STRONG Submitted by: G2P, PanelApp Australia, Labcorp Genetics (formerly Invitae)
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 -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.79).

BP6

Variant X-53394733-C-T is Benign according to our data. Variant chrX-53394733-C-T is described in ClinVar as Benign. ClinVar VariationId is 259962.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006306.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SMC1A	NM_006306.4	MANE Select	c.2973+45G>A		intron	N/A	NP_006297.2
	SMC1A	NM_001281463.1		c.2907+45G>A		intron	N/A	NP_001268392.1	G8JLG1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
SMC1A	ENST00000322213.9	TSL:1 MANE Select	c.2973+45G>A	intron	N/A	ENSP00000323421.3	Q14683
SMC1A	ENST00000375340.10	TSL:1	c.2907+45G>A	intron	N/A	ENSP00000364489.7	G8JLG1
SMC1A	ENST00000675504.1		c.2907+45G>A	intron	N/A	ENSP00000502524.1	G8JLG1

Frequencies

GnomAD3 genomes

AF:

0.0135

AC:

1417

AN:

105212

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00220

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00620

Gnomad ASJ

AF:

0.00235

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000441

Gnomad FIN

AF:

0.0360

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0211

Gnomad OTH

AF:

0.0122

GnomAD2 exomes

AF:

0.0200

AC:

2351

AN:

117285

AF XY:

0.0224

show subpopulations

Gnomad AFR exome

AF:

0.00273

Gnomad AMR exome

AF:

0.00671

Gnomad ASJ exome

AF:

0.00496

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0506

Gnomad NFE exome

AF:

0.0343

Gnomad OTH exome

AF:

0.0160

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.0277

AC:

9574

AN:

345873

Hom.:

616

Cov.:

AF XY:

0.0364

AC XY:

3821

AN XY:

104947

show subpopulations

African (AFR)

AF:

0.00333

AC:

AN:

10812

American (AMR)

AF:

0.00756

AC:

179

AN:

23675

Ashkenazi Jewish (ASJ)

AF:

0.00645

AC:

AN:

11626

East Asian (EAS)

AF:

0.00

AC:

AN:

20106

South Asian (SAS)

AF:

0.00127

AC:

AN:

35363

European-Finnish (FIN)

AF:

0.0496

AC:

1424

AN:

28717

Middle Eastern (MID)

AF:

0.0212

AC:

AN:

1321

European-Non Finnish (NFE)

AF:

0.0375

AC:

7349

AN:

195743

Other (OTH)

AF:

0.0237

AC:

438

AN:

18510

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.705

Heterozygous variant carriers

178

357

535

714

892

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

118

236

354

472

590

<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

Data not reliable, filtered out with message: AS_VQSR

AF:

0.0135

AC:

1417

AN:

105249

Hom.:

Cov.:

AF XY:

0.0146

AC XY:

408

AN XY:

28009

show subpopulations

African (AFR)

AF:

0.00219

AC:

AN:

28732

American (AMR)

AF:

0.00619

AC:

AN:

9696

Ashkenazi Jewish (ASJ)

AF:

0.00235

AC:

AN:

2553

East Asian (EAS)

AF:

0.00

AC:

AN:

3294

South Asian (SAS)

AF:

0.000443

AC:

AN:

2259

European-Finnish (FIN)

AF:

0.0360

AC:

191

AN:

5301

Middle Eastern (MID)

AF:

0.00

AC:

AN:

208

European-Non Finnish (NFE)

AF:

0.0211

AC:

1079

AN:

51126

Other (OTH)

AF:

0.0120

AC:

AN:

1416

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.622

Heterozygous variant carriers

137

182

228

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

100

<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:

0.0162

Hom.:

110

Bravo

AF:

0.0105

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

PhyloP100

-1.2

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over