dbSNP rs747185206: SMARCD1:p.Asn122Thr (chr12-50086348-A-C) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_003076.5(SMARCD1):c.365A>C(p.Asn122Thr) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000245 in 815,310 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/23 in silico tools predict a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 31)

Exomes 𝑓: 0.0000025 ( 0 hom. )

Consequence

SMARCD1
NM_003076.5 missense, splice_region

Scores

Splicing: ADA: 0.002846

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 3.34

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:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.14194122).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SMARCD1	NM_003076.5 link	c.365A>C	p.Asn122Thr	missense_variant, splice_region_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.365A>C	p.Asn122Thr	missense_variant, splice_region_variant	Exon 2 of 13	1	NM_003076.5	ENSP00000378414.4		Q96GM5-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000245

AC:

AN:

815310

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

415416

show subpopulations

Gnomad4 AFR exome

AF:

0.0000532

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:

0.00

Gnomad4 OTH exome

AF:

0.0000322

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.070

BayesDel_addAF

Benign

-0.15

BayesDel_noAF

Benign

-0.46

CADD

Uncertain

DANN

Benign

0.94

DEOGEN2

Benign

0.058

T;.;T;.;T

Eigen

Benign

-0.27

Eigen_PC

Benign

-0.062

FATHMM_MKL

Uncertain

0.96

LIST_S2

Uncertain

0.91

D;D;D;D;D

M_CAP

Benign

0.011

MetaRNN

Benign

0.14

T;T;T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.1

L;L;.;.;.

PrimateAI

Uncertain

0.58

PROVEAN

Benign

-0.36

N;N;N;N;N

REVEL

Benign

0.055

Sift

Benign

0.27

T;T;T;T;T

Sift4G

Benign

0.53

T;T;T;T;T

Polyphen

0.0050

B;B;.;.;.

Vest4

0.31

MutPred

0.36

Gain of phosphorylation at N122 (P = 0.0389);Gain of phosphorylation at N122 (P = 0.0389);Gain of phosphorylation at N122 (P = 0.0389);Gain of phosphorylation at N122 (P = 0.0389);.;

MVP

0.17

MPC

1.1

ClinPred

0.78

GERP RS

4.9

Varity_R

0.084

gMVP

0.47

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.0028

dbscSNV1_RF

Benign

0.094

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over