Variant 11-66341605-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_015399.4(BRMS1):c.158A>G(p.Tyr53Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000889 in 1,461,756 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000089 ( 0 hom. )

Consequence

BRMS1
NM_015399.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.47

Variant links:

Genes affected

BRMS1 (HGNC:17262): (BRMS1 transcriptional repressor and anoikis regulator) This gene reduces the metastatic potential, but not the tumorogenicity, of human breast cancer and melanoma cell lines. The protein encoded by this gene localizes primarily to the nucleus and is a component of the mSin3a family of histone deacetylase complexes (HDAC). The protein contains two coiled-coil motifs and several imperfect leucine zipper motifs. Alternative splicing results in two transcript variants encoding different isoforms. [provided by RefSeq, Jul 2008]

BRMS1 links:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.029024422).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
BRMS1	NM_015399.4 linkuse as main transcript	c.158A>G	p.Tyr53Cys	missense_variant	3/10	ENST00000359957.8
BRMS1	NM_001024957.2 linkuse as main transcript	c.158A>G	p.Tyr53Cys	missense_variant	3/10
BRMS1	XM_024448425.2 linkuse as main transcript	c.158A>G	p.Tyr53Cys	missense_variant	3/9
BRMS1	XM_024448426.2 linkuse as main transcript	c.158A>G	p.Tyr53Cys	missense_variant	3/9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
BRMS1	ENST00000359957.8 linkuse as main transcript	c.158A>G	p.Tyr53Cys	missense_variant	3/10	1	NM_015399.4	P1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000119

AC:

AN:

251306

Hom.:

AF XY:

0.0000147

AC XY:

AN XY:

135824

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000289

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000653

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000889

AC:

AN:

1461756

Hom.:

Cov.:

AF XY:

0.0000138

AC XY:

AN XY:

727182

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000224

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000812

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000360

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000756

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Feb 13, 2024

The c.158A>G (p.Y53C) alteration is located in exon 3 (coding exon 2) of the BRMS1 gene. This alteration results from a A to G substitution at nucleotide position 158, causing the tyrosine (Y) at amino acid position 53 to be replaced by a cysteine (C). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.071

BayesDel_addAF

Benign

-0.22

BayesDel_noAF

Benign

-0.38

CADD

Benign

DANN

Benign

0.83

DEOGEN2

Benign

0.0093

T;T;.

Eigen

Benign

-0.67

Eigen_PC

Benign

-0.44

FATHMM_MKL

Uncertain

0.80

LIST_S2

Benign

0.83

T;T;T

M_CAP

Benign

0.0019

MetaRNN

Benign

0.029

T;T;T

MetaSVM

Benign

-1.1

MutationTaster

Benign

0.85

D;D

PrimateAI

Uncertain

0.67

PROVEAN

Benign

7.8

N;N;N

REVEL

Benign

0.071

Sift

Benign

1.0

T;T;T

Sift4G

Benign

1.0

T;T;.

Polyphen

0.0

B;B;.

Vest4

0.19

MutPred

0.29

Loss of phosphorylation at Y53 (P = 0.0054);Loss of phosphorylation at Y53 (P = 0.0054);Loss of phosphorylation at Y53 (P = 0.0054);

MVP

0.42

MPC

0.21

ClinPred

0.23

GERP RS

2.1

Varity_R

0.30

gMVP

0.092

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over