14-35865750-T-C

Position:

• chr14-35865750-T-C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_032352.4(BRMS1L):​c.716T>C​(p.Val239Ala) 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 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: not found (cov: 32)
• Consequence: BRMS1L NM_032352.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.20

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.17420179).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
BRMS1L	NM_032352.4	c.716T>C	p.Val239Ala	missense_variant	8/10	ENST00000216807.12
BRMS1L	XM_005268128.2	c.716T>C	p.Val239Ala	missense_variant	8/10
BRMS1L	XM_047431806.1	c.572T>C	p.Val191Ala	missense_variant	10/12
BRMS1L	XM_017021705.1	c.572T>C	p.Val191Ala	missense_variant	8/10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
BRMS1L	ENST00000216807.12	c.716T>C	p.Val239Ala	missense_variant	8/10	1	NM_032352.4	P1
BRMS1L	ENST00000551774.1	c.461T>C	p.Val154Ala	missense_variant	6/8	1
BRMS1L	ENST00000548758.1	n.776T>C		non_coding_transcript_exon_variant	8/8	1
BRMS1L	ENST00000552677.5	c.*682T>C		3_prime_UTR_variant, NMD_transcript_variant	9/11	2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 17, 2023

The c.716T>C (p.V239A) alteration is located in exon 8 (coding exon 8) of the BRMS1L gene. This alteration results from a T to C substitution at nucleotide position 716, causing the valine (V) at amino acid position 239 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	Benign	0.14
BayesDel_addAF	Benign	-0.0037	T
BayesDel_noAF	Benign	-0.24
CADD	Benign	21
DANN	Benign	0.90
DEOGEN2	Benign	0.013	T
Eigen	Uncertain	0.19
Eigen_PC	Uncertain	0.33
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Benign	0.77	T
M_CAP	Benign	0.0030	T
MetaRNN	Benign	0.17	T
MetaSVM	Benign	-0.91	T
MutationAssessor	Benign	1.8	L
MutationTaster	Benign	1.0	D;D
PrimateAI	Pathogenic	0.83	D
PROVEAN	Benign	0.31	N
REVEL	Benign	0.094
Sift	Benign	0.58	T
Sift4G	Benign	0.76	T
Polyphen		0.012	B
Vest4		0.55
MutPred		0.32		Gain of catalytic residue at P243 (P = 0.0016);
MVP		0.56
MPC		0.75
ClinPred		0.58	D
GERP RS		5.9
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.095
gMVP		0.53

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.070		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: chr14-36334956;