rs1264011

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_006306.4(SMC1A):c.-19C>T variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.435 in 112,256 control chromosomes in the GnomAD database, including 9,273 homozygotes. There are 14,999 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.43 ( 9273 hom., 14999 hem., cov: 25)

Exomes 𝑓: 0.57 ( 115090 hom. 174600 hem. )

Failed GnomAD Quality Control

Consequence

SMC1A
NM_006306.4 5_prime_UTR_premature_start_codon_gain

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:8

Conservation

PhyloP100: 0.251

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:

RIBC1 (HGNC:26537): (RIB43A domain with coiled-coils 1)

RIBC1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.71).

BP6

Variant X-53422619-G-A is Benign according to our data. Variant chrX-53422619-G-A is described in ClinVar as [Benign]. Clinvar id is 95364.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chrX-53422619-G-A is described in Lovd as [Benign]. Variant chrX-53422619-G-A is described in Lovd as [Likely_benign].

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.587 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
SMC1A	NM_006306.4 link	c.-19C>T	5_prime_UTR_premature_start_codon_gain_variant	Exon 1 of 25	ENST00000322213.9	NP_006297.2	Q14683A0A384MR33Q68EN4
SMC1A	NM_006306.4 link	c.-19C>T	5_prime_UTR_variant	Exon 1 of 25	ENST00000322213.9	NP_006297.2	Q14683A0A384MR33Q68EN4
SMC1A	NM_001281463.1 link	c.-231C>T	5_prime_UTR_premature_start_codon_gain_variant	Exon 1 of 26		NP_001268392.1	G8JLG1
SMC1A	NM_001281463.1 link	c.-231C>T	5_prime_UTR_variant	Exon 1 of 26		NP_001268392.1	G8JLG1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SMC1A	ENST00000322213.9 link	c.-19C>T		5_prime_UTR_premature_start_codon_gain_variant	Exon 1 of 25	1	NM_006306.4	ENSP00000323421.3		Q14683
SMC1A	ENST00000322213.9 link	c.-19C>T		5_prime_UTR_variant	Exon 1 of 25	1	NM_006306.4	ENSP00000323421.3		Q14683

Frequencies

GnomAD3 genomes

AF:

0.435

AC:

48816

AN:

112202

Hom.:

9278

Cov.:

AF XY:

0.436

AC XY:

14989

AN XY:

34412

show subpopulations

Gnomad AFR

AF:

0.0885

Gnomad AMI

AF:

0.532

Gnomad AMR

AF:

0.506

Gnomad ASJ

AF:

0.505

Gnomad EAS

AF:

0.528

Gnomad SAS

AF:

0.436

Gnomad FIN

AF:

0.607

Gnomad MID

AF:

0.553

Gnomad NFE

AF:

0.592

Gnomad OTH

AF:

0.462

GnomAD3 exomes

AF:

0.523

AC:

94446

AN:

180723

Hom.:

16594

AF XY:

0.532

AC XY:

34869

AN XY:

65599

show subpopulations

Gnomad AFR exome

AF:

0.0779

Gnomad AMR exome

AF:

0.522

Gnomad ASJ exome

AF:

0.490

Gnomad EAS exome

AF:

0.534

Gnomad SAS exome

AF:

0.467

Gnomad FIN exome

AF:

0.601

Gnomad NFE exome

AF:

0.593

Gnomad OTH exome

AF:

0.550

GnomAD4 exome

Data not reliable, filtered out with message: InbreedingCoeff

AF:

0.573

AC:

572950

AN:

1000785

Hom.:

115090

Cov.:

AF XY:

0.595

AC XY:

174600

AN XY:

293349

show subpopulations

Gnomad4 AFR exome

AF:

0.0789

Gnomad4 AMR exome

AF:

0.518

Gnomad4 ASJ exome

AF:

0.501

Gnomad4 EAS exome

AF:

0.505

Gnomad4 SAS exome

AF:

0.470

Gnomad4 FIN exome

AF:

0.607

Gnomad4 NFE exome

AF:

0.602

Gnomad4 OTH exome

AF:

0.545

GnomAD4 genome

AF:

0.435

AC:

48818

AN:

112256

Hom.:

9273

Cov.:

AF XY:

0.435

AC XY:

14999

AN XY:

34476

show subpopulations

Gnomad4 AFR

AF:

0.0884

Gnomad4 AMR

AF:

0.506

Gnomad4 ASJ

AF:

0.505

Gnomad4 EAS

AF:

0.529

Gnomad4 SAS

AF:

0.437

Gnomad4 FIN

AF:

0.607

Gnomad4 NFE

AF:

0.592

Gnomad4 OTH

AF:

0.460

Alfa

AF:

0.509

Hom.:

6264

Bravo

AF:

0.417

ClinVar

Significance: Benign

Submissions summary: Benign:8

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:3

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Aug 18, 2014

Eurofins Ntd Llc (ga)

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Jul 15, 2024

Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is classified as Benign based on local population frequency. This variant was detected in 38% of patients studied in a panel designed for Epileptic and Developmental Encephalopathy and Progressive Myoclonus Epilepsy. Number of patients: 35. Only high quality variants are reported. -

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Mar 03, 2015

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Developmental and epileptic encephalopathy, 85, with or without midline brain defects

Benign:1

Jul 15, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Congenital muscular hypertrophy-cerebral syndrome

Benign:1

Jul 15, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

De Lange syndrome

Benign:1

Jun 14, 2016

Illumina Laboratory Services, Illumina

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.71

CADD

Benign

6.2

DANN

Benign

0.93

RBP_binding_hub_radar

0.92

RBP_regulation_power_radar

3.1

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