Variant 14-35826548-A-C details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_032352.4(BRMS1L):c.32A>C(p.Glu11Ala) variant causes a missense change. The variant allele was found at a frequency of 0.000005 in 1,601,512 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0000048 ( 0 hom. )

Consequence

BRMS1L
NM_032352.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.04

Variant links:

Genes affected

BRMS1L (HGNC:20512): (BRMS1 like transcriptional repressor) The protein encoded by this gene shows sequence similarity to the human breast carcinoma metastasis suppressor (BRMS1) protein and the mammalian Sds3 (suppressor of defective silencing 3) proteins. This protein is a component of the mSin3a family of histone deacetylase complexes (HDAC). [provided by RefSeq, Jul 2008]

BRMS1L links:

BRMS1L (HGNC:):

BRMS1L links:

Genome browser will be placed here

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=0.27355748).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
BRMS1L	NM_032352.4 linkuse as main transcript	c.32A>C	p.Glu11Ala	missense_variant	1/10	ENST00000216807.12	NP_115728.2	Q5PSV4-1
BRMS1L	XM_005268128.2 linkuse as main transcript	c.32A>C	p.Glu11Ala	missense_variant	1/10		XP_005268185.1
BRMS1L	XM_047431806.1 linkuse as main transcript	c.-326A>C		5_prime_UTR_variant	1/12		XP_047287762.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
BRMS1L	ENST00000216807.12 linkuse as main transcript	c.32A>C	p.Glu11Ala	missense_variant	1/10	1	NM_032352.4	ENSP00000216807.6		Q5PSV4-1

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152222

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.00000877

AC:

AN:

227922

Hom.:

AF XY:

0.00000814

AC XY:

AN XY:

122782

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000316

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000969

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000483

AC:

AN:

1449290

Hom.:

Cov.:

AF XY:

0.00000695

AC XY:

AN XY:

719458

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:

0.00000542

Gnomad4 OTH exome

AF:

0.0000167

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152222

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74360

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000936

Hom.:

Bravo

AF:

0.00000378

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

Sep 08, 2024

The c.32A>C (p.E11A) alteration is located in exon 1 (coding exon 1) of the BRMS1L gene. This alteration results from a A to C substitution at nucleotide position 32, causing the glutamic acid (E) at amino acid position 11 to be replaced by an alanine (A). 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

Uncertain

0.38

BayesDel_addAF

Benign

-0.026

BayesDel_noAF

Benign

-0.17

CADD

Pathogenic

DANN

Benign

0.95

DEOGEN2

Benign

0.045

Eigen

Uncertain

0.45

Eigen_PC

Uncertain

0.53

FATHMM_MKL

Uncertain

0.89

LIST_S2

Benign

0.76

M_CAP

Benign

0.013

MetaRNN

Benign

0.27

MetaSVM

Benign

-0.73

MutationAssessor

Benign

2.0

PrimateAI

Pathogenic

0.85

PROVEAN

Benign

-1.9

REVEL

Uncertain

0.31

Sift

Uncertain

0.017

Sift4G

Benign

0.39

Polyphen

0.96

Vest4

0.25

MutPred

0.32

Gain of MoRF binding (P = 0.0137);

MVP

0.47

MPC

0.90

ClinPred

0.83

GERP RS

5.4

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.6

Varity_R

0.52

gMVP

0.13

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.

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