Genetic Variant NM_003076.5:c.89C>G (chr12-50085458-C-G) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

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

The NM_003076.5(SMARCD1):c.89C>G(p.Pro30Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000276 in 1,087,178 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 31)

Exomes 𝑓: 0.0000028 ( 0 hom. )

Consequence

SMARCD1
NM_003076.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 3.55

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 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SMARCD1	NM_003076.5 link	c.89C>G	p.Pro30Arg	missense_variant	Exon 1 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.89C>G	p.Pro30Arg	missense_variant	Exon 1 of 13	1	NM_003076.5	ENSP00000378414.4		Q96GM5-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000276

AC:

AN:

1087178

Hom.:

Cov.:

AF XY:

0.00000194

AC XY:

AN XY:

514538

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:

0.00000325

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.26

BayesDel_addAF

Pathogenic

0.20

BayesDel_noAF

Uncertain

0.040

CADD

Benign

DANN

Benign

0.92

DEOGEN2

Benign

0.052

T;.;T;.

Eigen

Benign

-0.17

Eigen_PC

Benign

-0.18

FATHMM_MKL

Benign

0.56

LIST_S2

Benign

0.74

T;T;T;T

M_CAP

Pathogenic

0.99

MetaRNN

Uncertain

0.45

T;T;T;T

MetaSVM

Uncertain

0.56

MutationAssessor

Benign

1.0

L;L;.;.

PrimateAI

Pathogenic

0.95

PROVEAN

Benign

-1.1

N;N;N;N

REVEL

Uncertain

0.58

Sift

Benign

0.34

T;T;T;D

Sift4G

Benign

0.25

T;T;T;T

Polyphen

0.53

P;P;.;.

Vest4

0.49

MutPred

0.28

Gain of methylation at P30 (P = 8e-04);Gain of methylation at P30 (P = 8e-04);Gain of methylation at P30 (P = 8e-04);Gain of methylation at P30 (P = 8e-04);

MVP

0.56

MPC

1.1

ClinPred

0.77

GERP RS

2.3

Varity_R

0.16

gMVP

0.12

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over