Variant chr12-50085527-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 3P and 1B. PM2PP2BP4

The NM_003076.5(SMARCD1):c.158T>C(p.Met53Thr) variant causes a missense change. The variant allele was found at a frequency of 0.00000246 in 1,221,024 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000014 ( 0 hom., cov: 30)

Exomes 𝑓: 9.3e-7 ( 0 hom. )

Consequence

SMARCD1
NM_003076.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.79

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 Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP2

Missense variant in gene, where missense usually causes diseases (based on misZ statistic), SMARCD1. . Gene score misZ 3.4416 (greater than the threshold 3.09). Trascript score misZ 3.2646 (greater than threshold 3.09). GenCC has associacion of gene with Coffin-Siris syndrome 11, autism, susceptibility to, 15, Coffin-Siris syndrome.

BP4

Computational evidence support a benign effect (MetaRNN=0.3109706).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SMARCD1	NM_003076.5 linkuse as main transcript	c.158T>C	p.Met53Thr	missense_variant	1/13	ENST00000394963.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SMARCD1	ENST00000394963.9 linkuse as main transcript	c.158T>C	p.Met53Thr	missense_variant	1/13	1	NM_003076.5	P1	Q96GM5-1

Frequencies

GnomAD3 genomes

AF:

0.0000135

AC:

AN:

148076

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000200

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

9.32e-7

AC:

AN:

1072948

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

506896

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000109

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000135

AC:

AN:

148076

Hom.:

Cov.:

AF XY:

0.0000278

AC XY:

AN XY:

72068

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.000200

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

GeneDx

Dec 04, 2022

Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.16

BayesDel_addAF

Uncertain

0.12

BayesDel_noAF

Uncertain

-0.070

CADD

Uncertain

DANN

Benign

0.92

DEOGEN2

Benign

0.043

T;.;T;.

Eigen

Benign

-0.23

Eigen_PC

Benign

-0.062

FATHMM_MKL

Benign

0.61

LIST_S2

Benign

0.74

T;T;T;T

M_CAP

Pathogenic

0.99

MetaRNN

Benign

0.31

T;T;T;T

MetaSVM

Benign

-0.53

MutationAssessor

Benign

1.5

L;L;.;.

MutationTaster

Benign

1.0

D;D

PrimateAI

Pathogenic

0.95

PROVEAN

Benign

-0.39

N;N;N;N

REVEL

Benign

0.25

Sift

Benign

0.37

T;T;T;D

Sift4G

Benign

0.38

T;T;T;T

Polyphen

0.0040

B;B;.;.

Vest4

0.41

MutPred

0.28

Gain of phosphorylation at M53 (P = 0.0017);Gain of phosphorylation at M53 (P = 0.0017);Gain of phosphorylation at M53 (P = 0.0017);Gain of phosphorylation at M53 (P = 0.0017);

MVP

0.60

MPC

1.2

ClinPred

0.70

GERP RS

4.7

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.44

gMVP

0.22

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