12-50086261-A-G

Variant names:

• chr12-50086261-A-G
• NM_003076.5:c.278A>G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_003076.5(SMARCD1):​c.278A>G​(p.Gln93Arg) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 31)
• Consequence: SMARCD1 NM_003076.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.39

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]

ACMG classification

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=0.13931507).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SMARCD1	NM_003076.5	c.278A>G	p.Gln93Arg	missense_variant	Exon 2 of 13	ENST00000394963.9	NP_003067.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SMARCD1	ENST00000394963.9	c.278A>G	p.Gln93Arg	missense_variant	Exon 2 of 13	1	NM_003076.5	ENSP00000378414.4

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 31

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Uncertain:1

Feb 04, 2024

GeneDx

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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	Uncertain	0.42
BayesDel_addAF	Benign	-0.0019	T
BayesDel_noAF	Benign	-0.24
CADD	Uncertain	25
DANN	Benign	0.88
DEOGEN2	Benign	0.078	T;.;T;.;T
Eigen	Benign	-0.23
Eigen_PC	Benign	-0.080
FATHMM_MKL	Uncertain	0.86	D
LIST_S2	Uncertain	0.88	D;D;D;D;D
M_CAP	Benign	0.041	D
MetaRNN	Benign	0.14	T;T;T;T;T
MetaSVM	Benign	-0.53	T
MutationAssessor	Benign	0.69	N;N;.;.;.
PrimateAI	Uncertain	0.55	T
PROVEAN	Benign	-0.77	N;N;N;N;N
REVEL	Benign	0.23
Sift	Benign	0.41	T;T;T;T;T
Sift4G	Benign	0.49	T;T;T;T;T
Polyphen		0.24	B;B;.;.;.
Vest4		0.58
MutPred		0.28		Gain of MoRF binding (P = 0.0245);Gain of MoRF binding (P = 0.0245);Gain of MoRF binding (P = 0.0245);Gain of MoRF binding (P = 0.0245);.;
MVP		0.41
MPC		1.1
ClinPred		0.39	T
GERP RS		4.1
Varity_R		0.17
gMVP		0.57

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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.

Other links and lift over

hg19: chr12-50480044;