X-129448390-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_001282874.2(SMARCA1):​c.3084G>A​(p.Met1028Ile) variant causes a missense change. The variant allele was found at a frequency of 0.000000924 in 1,081,949 control chromosomes in the GnomAD database, with no homozygous occurrence. There are no hemizygote samples in GnomAD. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. M1028V) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 22)
Exomes 𝑓: 9.2e-7 ( 0 hom. 0 hem. )

Consequence

SMARCA1
NM_001282874.2 missense

Scores

1
7
9

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 5.33
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 Uncertain_significance. Variant got 1 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.31709152).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
SMARCA1NM_001282874.2 linkc.3084G>A p.Met1028Ile missense_variant Exon 24 of 25 ENST00000371121.5 NP_001269803.1 B7ZLQ5

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
SMARCA1ENST00000371121.5 linkc.3084G>A p.Met1028Ile missense_variant Exon 24 of 25 1 NM_001282874.2 ENSP00000360162.4 B7ZLQ5
SMARCA1ENST00000371123.5 linkc.3048G>A p.Met1016Ile missense_variant Exon 23 of 24 1 ENSP00000360164.2 A0A0A0MRP6
SMARCA1ENST00000371122.8 linkc.3084G>A p.Met1028Ile missense_variant Exon 24 of 25 1 ENSP00000360163.4 P28370-1
SMARCA1ENST00000617310.4 linkn.3402G>A non_coding_transcript_exon_variant Exon 22 of 23 2

Frequencies

GnomAD3 genomes
Cov.:
22
GnomAD3 exomes
AF:
0.00000550
AC:
1
AN:
181893
Hom.:
0
AF XY:
0.00
AC XY:
0
AN XY:
66549
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.000134
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
9.24e-7
AC:
1
AN:
1081949
Hom.:
0
Cov.:
26
AF XY:
0.00
AC XY:
0
AN XY:
348631
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.0000519
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:
0.00
GnomAD4 genome
Cov.:
22

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Uncertain
0.45
BayesDel_addAF
Uncertain
0.069
T
BayesDel_noAF
Benign
-0.14
CADD
Uncertain
23
DANN
Benign
0.96
DEOGEN2
Benign
0.063
T;T;.
FATHMM_MKL
Uncertain
0.92
D
LIST_S2
Uncertain
0.95
D;D;D
M_CAP
Pathogenic
0.43
D
MetaRNN
Benign
0.32
T;T;T
MetaSVM
Uncertain
-0.073
T
MutationAssessor
Benign
0.41
N;.;.
PrimateAI
Uncertain
0.76
T
PROVEAN
Benign
-1.4
N;N;.
REVEL
Uncertain
0.30
Sift
Benign
0.21
T;T;.
Sift4G
Benign
0.20
T;T;T
Polyphen
0.059
B;.;B
Vest4
0.37
MutPred
0.47
Loss of disorder (P = 0.199);.;Loss of disorder (P = 0.199);
MVP
0.78
MPC
0.73
ClinPred
0.30
T
GERP RS
5.9
Varity_R
0.58
gMVP
0.40

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs147306232; hg19: chrX-128582367; API