chrX-129465529-C-A

Variant summary

Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2PP3_Strong

The NM_001282874.2(SMARCA1):​c.3021G>T​(p.Arg1007Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. R1007R) has been classified as Likely benign.

Frequency

Genomes: not found (cov: 23)

Consequence

SMARCA1
NM_001282874.2 missense

Scores

12
4
1

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.70
Variant links:
Genes affected
SMARCA1 (HGNC:11097): (SWI/SNF related, matrix associated, actin dependent regulator of chromatin, subfamily a, member 1) This gene encodes a member of the SWI/SNF family of proteins. The encoded protein is an ATPase which is expressed in diverse tissues and contributes to the chromatin remodeling complex that is involved in transcription. The protein may also play a role in DNA damage, growth inhibition and apoptosis of cancer cells. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Sep 2013]

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ACMG classification

Classification made for transcript

Verdict is Likely_pathogenic. Variant got 6 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.948

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
SMARCA1NM_001282874.2 linkc.3021G>T p.Arg1007Ser missense_variant Exon 23 of 25 ENST00000371121.5 NP_001269803.1 B7ZLQ5

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
SMARCA1ENST00000371121.5 linkc.3021G>T p.Arg1007Ser missense_variant Exon 23 of 25 1 NM_001282874.2 ENSP00000360162.4 B7ZLQ5
SMARCA1ENST00000371123.5 linkc.2985G>T p.Arg995Ser missense_variant Exon 22 of 24 1 ENSP00000360164.2 A0A0A0MRP6
SMARCA1ENST00000371122.8 linkc.3021G>T p.Arg1007Ser missense_variant Exon 23 of 25 1 ENSP00000360163.4 P28370-1
SMARCA1ENST00000617310.4 linkn.3339G>T non_coding_transcript_exon_variant Exon 21 of 23 2

Frequencies

GnomAD3 genomes
Cov.:
23
GnomAD4 exome
Cov.:
26
GnomAD4 genome
Cov.:
23

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
1.0
BayesDel_addAF
Pathogenic
0.48
D
BayesDel_noAF
Pathogenic
0.45
CADD
Uncertain
24
DANN
Uncertain
1.0
DEOGEN2
Uncertain
0.46
T;T;.
FATHMM_MKL
Uncertain
0.85
D
LIST_S2
Pathogenic
1.0
D;D;D
M_CAP
Pathogenic
0.66
D
MetaRNN
Pathogenic
0.95
D;D;D
MetaSVM
Pathogenic
0.86
D
MutationAssessor
Pathogenic
3.9
H;.;.
PrimateAI
Pathogenic
0.87
D
PROVEAN
Pathogenic
-5.4
D;D;.
REVEL
Pathogenic
0.90
Sift
Pathogenic
0.0
D;D;.
Sift4G
Uncertain
0.0020
D;D;D
Polyphen
1.0
D;.;D
Vest4
0.74
MutPred
0.86
Loss of MoRF binding (P = 0.0371);.;Loss of MoRF binding (P = 0.0371);
MVP
0.98
MPC
1.7
ClinPred
1.0
D
GERP RS
3.3
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7
Varity_R
0.96
gMVP
0.97

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: chrX-128599506; API