Variant rs2430853 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_015295.3(SMCHD1):c.174G>C(p.Ala58=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.563 in 1,489,176 control chromosomes in the GnomAD database, including 241,052 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Synonymous variant affecting the same amino acid position (i.e. A58A) has been classified as Pathogenic.

Frequency

Genomes: 𝑓 0.63 ( 32063 hom., cov: 33)

Exomes 𝑓: 0.55 ( 208989 hom. )

Consequence

SMCHD1
NM_015295.3 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:7

Conservation

PhyloP100: -0.813

Variant links:

Genes affected

SMCHD1 (HGNC:29090): (structural maintenance of chromosomes flexible hinge domain containing 1) This gene encodes a protein which contains a hinge region domain found in members of the SMC (structural maintenance of chromosomes) protein family. [provided by RefSeq, Dec 2011]

SMCHD1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.85).

BP6

Variant 18-2656249-G-C is Benign according to our data. Variant chr18-2656249-G-C is described in ClinVar as [Benign]. Clinvar id is 260632.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr18-2656249-G-C is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=-0.813 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.842 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SMCHD1	NM_015295.3 linkuse as main transcript	c.174G>C	p.Ala58=	synonymous_variant	1/48	ENST00000320876.11	NP_056110.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SMCHD1	ENST00000320876.11 linkuse as main transcript	c.174G>C	p.Ala58=	synonymous_variant	1/48	5	NM_015295.3	ENSP00000326603	P2	A6NHR9-1
SMCHD1	ENST00000688342.1 linkuse as main transcript	c.174G>C	p.Ala58=	synonymous_variant	1/47			ENSP00000508422	A2
SMCHD1	ENST00000684915.1 linkuse as main transcript	n.331G>C		non_coding_transcript_exon_variant	1/14

Frequencies

GnomAD3 genomes

AF:

0.633

AC:

96332

AN:

152064

Hom.:

32011

Cov.:

show subpopulations

Gnomad AFR

AF:

0.849

Gnomad AMI

AF:

0.646

Gnomad AMR

AF:

0.575

Gnomad ASJ

AF:

0.655

Gnomad EAS

AF:

0.343

Gnomad SAS

AF:

0.639

Gnomad FIN

AF:

0.570

Gnomad MID

AF:

0.672

Gnomad NFE

AF:

0.545

Gnomad OTH

AF:

0.631

GnomAD3 exomes

AF:

0.558

AC:

82317

AN:

147528

Hom.:

23631

AF XY:

0.557

AC XY:

46456

AN XY:

83462

show subpopulations

Gnomad AFR exome

AF:

0.851

Gnomad AMR exome

AF:

0.539

Gnomad ASJ exome

AF:

0.640

Gnomad EAS exome

AF:

0.319

Gnomad SAS exome

AF:

0.621

Gnomad FIN exome

AF:

0.547

Gnomad NFE exome

AF:

0.533

Gnomad OTH exome

AF:

0.565

GnomAD4 exome

AF:

0.555

AC:

741595

AN:

1336994

Hom.:

208989

Cov.:

AF XY:

0.557

AC XY:

368498

AN XY:

661722

show subpopulations

Gnomad4 AFR exome

AF:

0.873

Gnomad4 AMR exome

AF:

0.554

Gnomad4 ASJ exome

AF:

0.655

Gnomad4 EAS exome

AF:

0.334

Gnomad4 SAS exome

AF:

0.631

Gnomad4 FIN exome

AF:

0.554

Gnomad4 NFE exome

AF:

0.545

Gnomad4 OTH exome

AF:

0.575

GnomAD4 genome

AF:

0.634

AC:

96443

AN:

152182

Hom.:

32063

Cov.:

AF XY:

0.632

AC XY:

47043

AN XY:

74388

show subpopulations

Gnomad4 AFR

AF:

0.849

Gnomad4 AMR

AF:

0.576

Gnomad4 ASJ

AF:

0.655

Gnomad4 EAS

AF:

0.342

Gnomad4 SAS

AF:

0.638

Gnomad4 FIN

AF:

0.570

Gnomad4 NFE

AF:

0.545

Gnomad4 OTH

AF:

0.631

Alfa

AF:

0.448

Hom.:

1129

Bravo

AF:

0.642

Asia WGS

AF:

0.520

AC:

1810

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:7

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Benign, criteria provided, single submitter	clinical testing	Athena Diagnostics	Dec 18, 2018	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Mar 29, 2021	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

not specified

Benign:2

Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -
Benign, criteria provided, single submitter	clinical testing	Eurofins Ntd Llc (ga)	Mar 23, 2016	- -

Facioscapulohumeral muscular dystrophy 2

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Feb 01, 2024

- -

Arrhinia with choanal atresia and microphthalmia syndrome

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 15, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.85

CADD

Benign

6.1

DANN

Benign

0.51

RBP_binding_hub_radar

0.92

RBP_regulation_power_radar

2.1

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