Variant X-53374723-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2

The ENST00000322213.9(SMC1A):c.*5380G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00814 in 112,511 control chromosomes in the GnomAD database, including 6 homozygotes. There are 279 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0081 ( 6 hom., 277 hem., cov: 22)

Exomes 𝑓: 0.011 ( 0 hom. 2 hem. )

Consequence

SMC1A
ENST00000322213.9 3_prime_UTR

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.799

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 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.54).

BP6

Variant X-53374723-C-T is Benign according to our data. Variant chrX-53374723-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 368546.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.00813 (912/112155) while in subpopulation SAS AF= 0.0368 (99/2691). AF 95% confidence interval is 0.0309. There are 6 homozygotes in gnomad4. There are 277 alleles in male gnomad4 subpopulation. Median coverage is 22. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 6 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SMC1A	NM_006306.4 linkuse as main transcript	c.*5380G>A		3_prime_UTR_variant	25/25	ENST00000322213.9	NP_006297.2
SMC1A	NM_001281463.1 linkuse as main transcript	c.*5380G>A		3_prime_UTR_variant	26/26		NP_001268392.1

Ensembl

Gene	Transcript	HGVSc	Effect	#exon/exons	TSL	MANE	Protein	Appris
SMC1A	ENST00000322213.9 linkuse as main transcript	c.*5380G>A	3_prime_UTR_variant	25/25	1	NM_006306.4	ENSP00000323421	P1
SMC1A	ENST00000375340.10 linkuse as main transcript	c.*5380G>A	3_prime_UTR_variant	26/26	1		ENSP00000364489
SMC1A	ENST00000675504.1 linkuse as main transcript	c.*5380G>A	3_prime_UTR_variant	25/25			ENSP00000502524

Frequencies

GnomAD3 genomes

AF:

0.00816

AC:

915

AN:

112102

Hom.:

Cov.:

AF XY:

0.00815

AC XY:

279

AN XY:

34246

show subpopulations

Gnomad AFR

AF:

0.00110

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00634

Gnomad ASJ

AF:

0.0121

Gnomad EAS

AF:

0.000278

Gnomad SAS

AF:

0.0374

Gnomad FIN

AF:

0.00816

Gnomad MID

AF:

0.0167

Gnomad NFE

AF:

0.0116

Gnomad OTH

AF:

0.00663

GnomAD4 exome

AF:

0.0112

AC:

AN:

356

Hom.:

Cov.:

AF XY:

0.0139

AC XY:

AN XY:

144

show subpopulations

Gnomad4 FIN exome

AF:

0.0119

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.00813

AC:

912

AN:

112155

Hom.:

Cov.:

AF XY:

0.00807

AC XY:

277

AN XY:

34309

show subpopulations

Gnomad4 AFR

AF:

0.00110

Gnomad4 AMR

AF:

0.00634

Gnomad4 ASJ

AF:

0.0121

Gnomad4 EAS

AF:

0.000278

Gnomad4 SAS

AF:

0.0368

Gnomad4 FIN

AF:

0.00816

Gnomad4 NFE

AF:

0.0116

Gnomad4 OTH

AF:

0.00654

Alfa

AF:

0.0108

Hom.:

Bravo

AF:

0.00730

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

De Lange syndrome

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.54

CADD

Benign

DANN

Benign

0.81

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over