12-50086319-G-T

Variant names:

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_003076.5(SMARCD1):c.336G>T(p.Gln112His) variant causes a missense change. The variant allele was found at a frequency of 0.00352 in 1,560,100 control chromosomes in the GnomAD database, including 7 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0025 ( 0 hom., cov: 31)

Exomes 𝑓: 0.0036 ( 7 hom. )

Consequence

SMARCD1
NM_003076.5 missense

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 4.20

Variant links:

Genes affected

SMARCD1 (HGNC:11106): (SWI/SNF related, matrix associated, actin dependent regulator of chromatin, subfamily d, member 1) The protein encoded by this gene is a member of the SWI/SNF family of proteins, whose members display helicase and ATPase activities and which are thought to regulate transcription of certain genes by altering the chromatin structure around those genes. The encoded protein is part of the large ATP-dependent chromatin remodeling complex SNF/SWI and has sequence similarity to the yeast Swp73 protein. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

SMARCD1 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 (MetaRNN=0.010879189).

BP6

Variant 12-50086319-G-T is Benign according to our data. Variant chr12-50086319-G-T is described in ClinVar as [Likely_benign]. Clinvar id is 2642976.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00247 (372/150528) while in subpopulation NFE AF= 0.00447 (302/67502). AF 95% confidence interval is 0.00406. There are 0 homozygotes in gnomad4. There are 171 alleles in male gnomad4 subpopulation. Median coverage is 31. This position pass quality control queck.

BS2

High AC in GnomAd4 at 372 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SMARCD1	NM_003076.5 link	c.336G>T	p.Gln112His	missense_variant	Exon 2 of 13	ENST00000394963.9	NP_003067.3	Q96GM5-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SMARCD1	ENST00000394963.9 link	c.336G>T	p.Gln112His	missense_variant	Exon 2 of 13	1	NM_003076.5	ENSP00000378414.4		Q96GM5-1

Frequencies

GnomAD3 genomes

AF:

0.00247

AC:

372

AN:

150412

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000607

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00112

Gnomad ASJ

AF:

0.00233

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000428

Gnomad FIN

AF:

0.00158

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00447

Gnomad OTH

AF:

0.000960

GnomAD3 exomes

AF:

0.00279

AC:

672

AN:

241002

Hom.:

AF XY:

0.00276

AC XY:

361

AN XY:

130582

show subpopulations

Gnomad AFR exome

AF:

0.000935

Gnomad AMR exome

AF:

0.000527

Gnomad ASJ exome

AF:

0.00252

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000948

Gnomad FIN exome

AF:

0.00133

Gnomad NFE exome

AF:

0.00502

Gnomad OTH exome

AF:

0.00224

GnomAD4 exome

AF:

0.00363

AC:

5114

AN:

1409572

Hom.:

Cov.:

AF XY:

0.00356

AC XY:

2498

AN XY:

701032

show subpopulations

Gnomad4 AFR exome

AF:

0.000782

Gnomad4 AMR exome

AF:

0.000650

Gnomad4 ASJ exome

AF:

0.00283

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00102

Gnomad4 FIN exome

AF:

0.00143

Gnomad4 NFE exome

AF:

0.00434

Gnomad4 OTH exome

AF:

0.00245

GnomAD4 genome

AF:

0.00247

AC:

372

AN:

150528

Hom.:

Cov.:

AF XY:

0.00232

AC XY:

171

AN XY:

73616

show subpopulations

Gnomad4 AFR

AF:

0.000605

Gnomad4 AMR

AF:

0.00112

Gnomad4 ASJ

AF:

0.00233

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000428

Gnomad4 FIN

AF:

0.00158

Gnomad4 NFE

AF:

0.00447

Gnomad4 OTH

AF:

0.000950

Alfa

AF:

0.00371

Hom.:

Bravo

AF:

0.00233

TwinsUK

AF:

0.00378

AC:

ALSPAC

AF:

0.00493

AC:

ESP6500AA

AF:

0.00113

AC:

ESP6500EA

AF:

0.00442

AC:

ExAC

AF:

0.00287

AC:

349

Asia WGS

AF:

0.00144

AC:

AN:

3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Coffin-Siris syndrome 11

Benign:1

May 04, 2023

Molecular Genetics, Royal Melbourne Hospital

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

European Non-Finnish population allele frequency is 0.4668% (rs139120093, 627/124688 alleles, 2 homozygotes in gnomAD v2.1). Based on the classification scheme RMH Modified ACMG/AMP Guidelines v1.5.1, this variant is classified as LIKELY BENIGN. Following criteria are met: BS1 -

not provided

Benign:1

Feb 01, 2025

CeGaT Center for Human Genetics Tuebingen

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

SMARCD1: PP2, BS1, BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.24

BayesDel_addAF

Benign

-0.19

BayesDel_noAF

Uncertain

-0.040

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.091

T;.;T;.;T

Eigen

Uncertain

0.30

Eigen_PC

Uncertain

0.32

FATHMM_MKL

Uncertain

0.96

LIST_S2

Uncertain

0.91

D;D;D;D;D

M_CAP

Benign

0.080

MetaRNN

Benign

0.011

T;T;T;T;T

MetaSVM

Uncertain

0.36

MutationAssessor

Uncertain

2.5

M;M;.;.;.

PrimateAI

Uncertain

0.78

PROVEAN

Benign

-1.3

N;N;N;N;N

REVEL

Uncertain

0.47

Sift

Uncertain

0.010

D;D;T;D;T

Sift4G

Uncertain

0.028

D;D;D;D;D

Polyphen

0.010

B;D;.;.;.

Vest4

0.60

MutPred

0.35

Gain of helix (P = 0.0143);Gain of helix (P = 0.0143);Gain of helix (P = 0.0143);Gain of helix (P = 0.0143);.;

MVP

0.72

MPC

1.0

ClinPred

0.040

GERP RS

4.2

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.8

Varity_R

0.15

gMVP

0.79

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