12-50086824-G-T

Position:

• chr12-50086824-G-T

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP2

The ENST00000394963.9(SMARCD1):​c.477G>T​(p.Gln159His) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: SMARCD1 ENST00000394963.9 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 6.86

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 3 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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SMARCD1	NM_003076.5	c.477G>T	p.Gln159His	missense_variant	4/13	ENST00000394963.9	NP_003067.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SMARCD1	ENST00000394963.9	c.477G>T	p.Gln159His	missense_variant	4/13	1	NM_003076.5	ENSP00000378414	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.71
BayesDel_addAF	Uncertain	0.12	D
BayesDel_noAF	Uncertain	-0.070
CADD	Pathogenic	28
DANN	Uncertain	1.0
DEOGEN2	Benign	0.13	T;.;T;.;T
Eigen	Pathogenic	0.72
Eigen_PC	Pathogenic	0.71
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.90	D;D;D;D;D
M_CAP	Benign	0.026	D
MetaRNN	Uncertain	0.55	D;D;D;D;D
MetaSVM	Benign	-0.74	T
MutationAssessor	Uncertain	2.6	M;M;.;.;.
MutationTaster	Benign	1.0	D;D
PrimateAI	Pathogenic	0.87	D
PROVEAN	Benign	-1.9	N;N;N;N;N
REVEL	Benign	0.26
Sift	Uncertain	0.0050	D;D;D;D;D
Sift4G	Uncertain	0.033	D;T;T;D;D
Polyphen		0.96	D;D;.;.;.
Vest4		0.58
MutPred		0.42		Loss of disorder (P = 0.0623);Loss of disorder (P = 0.0623);Loss of disorder (P = 0.0623);Loss of disorder (P = 0.0623);.;
MVP		0.56
MPC		1.8
ClinPred		0.93	D
GERP RS		4.3
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.71
gMVP		0.89

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr12-50480607;