Variant rs12327477 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.3528A>G(p.Thr1176=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.304 in 1,577,326 control chromosomes in the GnomAD database, including 76,454 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.30 ( 6927 hom., cov: 32)

Exomes 𝑓: 0.30 ( 69527 hom. )

Consequence

SMCHD1
NM_015295.3 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: 0.857

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:

(HGNC:):

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=-0.57).

BP6

Variant 18-2740716-A-G is Benign according to our data. Variant chr18-2740716-A-G is described in ClinVar as [Benign]. Clinvar id is 260643.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr18-2740716-A-G is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=0.857 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.48 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.3528A>G	p.Thr1176=	synonymous_variant	28/48	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.3528A>G	p.Thr1176=	synonymous_variant	28/48	5	NM_015295.3	ENSP00000326603	P2	A6NHR9-1
	ENST00000583546.1 linkuse as main transcript	n.371-48836T>C		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes

AF:

0.297

AC:

45168

AN:

151840

Hom.:

6911

Cov.:

show subpopulations

Gnomad AFR

AF:

0.261

Gnomad AMI

AF:

0.458

Gnomad AMR

AF:

0.359

Gnomad ASJ

AF:

0.317

Gnomad EAS

AF:

0.496

Gnomad SAS

AF:

0.448

Gnomad FIN

AF:

0.266

Gnomad MID

AF:

0.253

Gnomad NFE

AF:

0.282

Gnomad OTH

AF:

0.304

GnomAD3 exomes

AF:

0.343

AC:

82694

AN:

241024

Hom.:

15462

AF XY:

0.340

AC XY:

44464

AN XY:

130648

show subpopulations

Gnomad AFR exome

AF:

0.267

Gnomad AMR exome

AF:

0.476

Gnomad ASJ exome

AF:

0.326

Gnomad EAS exome

AF:

0.506

Gnomad SAS exome

AF:

0.447

Gnomad FIN exome

AF:

0.266

Gnomad NFE exome

AF:

0.281

Gnomad OTH exome

AF:

0.311

GnomAD4 exome

AF:

0.305

AC:

434133

AN:

1425368

Hom.:

69527

Cov.:

AF XY:

0.307

AC XY:

217985

AN XY:

709618

show subpopulations

Gnomad4 AFR exome

AF:

0.257

Gnomad4 AMR exome

AF:

0.460

Gnomad4 ASJ exome

AF:

0.324

Gnomad4 EAS exome

AF:

0.465

Gnomad4 SAS exome

AF:

0.441

Gnomad4 FIN exome

AF:

0.265

Gnomad4 NFE exome

AF:

0.285

Gnomad4 OTH exome

AF:

0.318

GnomAD4 genome

AF:

0.298

AC:

45216

AN:

151958

Hom.:

6927

Cov.:

AF XY:

0.300

AC XY:

22249

AN XY:

74272

show subpopulations

Gnomad4 AFR

AF:

0.261

Gnomad4 AMR

AF:

0.359

Gnomad4 ASJ

AF:

0.317

Gnomad4 EAS

AF:

0.496

Gnomad4 SAS

AF:

0.447

Gnomad4 FIN

AF:

0.266

Gnomad4 NFE

AF:

0.282

Gnomad4 OTH

AF:

0.307

Alfa

AF:

0.289

Hom.:

3637

Bravo

AF:

0.307

Asia WGS

AF:

0.491

AC:

1696

AN:

3452

ClinVar

Significance: Benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Athena Diagnostics	Nov 02, 2018	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jul 09, 2019	- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

- -

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

-0.57

CADD

Benign

4.5

DANN

Benign

0.75

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