Variant chr14-35832998-G-A 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_032352.4(BRMS1L):c.254G>A(p.Ser85Asn) variant causes a missense change. The variant allele was found at a frequency of 0.0000992 in 1,612,676 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00011 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000098 ( 0 hom. )

Consequence

BRMS1L
NM_032352.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.34

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:

Genome browser will be placed here

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=0.0658454).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
BRMS1L	NM_032352.4 linkuse as main transcript	c.254G>A	p.Ser85Asn	missense_variant	3/10	ENST00000216807.12
BRMS1L	XM_005268128.2 linkuse as main transcript	c.254G>A	p.Ser85Asn	missense_variant	3/10
BRMS1L	XM_047431806.1 linkuse as main transcript	c.110G>A	p.Ser37Asn	missense_variant	5/12
BRMS1L	XM_017021705.1 linkuse as main transcript	c.110G>A	p.Ser37Asn	missense_variant	3/10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
BRMS1L	ENST00000216807.12 linkuse as main transcript	c.254G>A	p.Ser85Asn	missense_variant	3/10	1	NM_032352.4	P1	Q5PSV4-1

Frequencies

GnomAD3 genomes

AF:

0.000112

AC:

AN:

152166

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.000576

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000206

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000996

AC:

AN:

250908

Hom.:

AF XY:

0.000103

AC XY:

AN XY:

135642

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.000199

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000203

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000979

AC:

143

AN:

1460392

Hom.:

Cov.:

AF XY:

0.0000908

AC XY:

AN XY:

726522

show subpopulations

Gnomad4 AFR exome

AF:

0.0000299

Gnomad4 AMR exome

AF:

0.0000224

Gnomad4 ASJ exome

AF:

0.000230

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.0000187

Gnomad4 NFE exome

AF:

0.000118

Gnomad4 OTH exome

AF:

0.0000497

GnomAD4 genome

AF:

0.000112

AC:

AN:

152284

Hom.:

Cov.:

AF XY:

0.000121

AC XY:

AN XY:

74462

show subpopulations

Gnomad4 AFR

AF:

0.0000241

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.000576

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000206

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000214

Hom.:

Bravo

AF:

0.0000907

TwinsUK

AF:

0.00

AC:

ALSPAC

AF:

0.000519

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000233

AC:

ExAC

AF:

0.000115

AC:

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

Apr 04, 2024

The c.254G>A (p.S85N) alteration is located in exon 3 (coding exon 3) of the BRMS1L gene. This alteration results from a G to A substitution at nucleotide position 254, causing the serine (S) at amino acid position 85 to be replaced by an asparagine (N). 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

0.10

BayesDel_addAF

Benign

-0.38

BayesDel_noAF

Benign

-0.50

CADD

Benign

DANN

Benign

0.70

DEOGEN2

Benign

0.014

Eigen

Benign

-0.23

Eigen_PC

Benign

0.019

FATHMM_MKL

Uncertain

0.96

LIST_S2

Uncertain

0.88

M_CAP

Benign

0.0057

MetaRNN

Benign

0.066

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.14

MutationTaster

Benign

1.0

D;D

PrimateAI

Uncertain

0.70

PROVEAN

Benign

-0.53

REVEL

Benign

0.097

Sift

Benign

0.68

Sift4G

Benign

0.86

Polyphen

0.0030

Vest4

0.26

MVP

0.23

MPC

0.60

ClinPred

0.23

GERP RS

5.1

Varity_R

0.26

gMVP

0.25

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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