X-136490230-T-G

Position:

• chrX-136490230-T-G

Variant summary

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

The NM_001727.2(BRS3):​c.532T>G​(p.Phe178Val) 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. 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: 23)
• Consequence: BRS3 NM_001727.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.05

Genes affected

BRS3 (HGNC:1113): (bombesin receptor subtype 3) The protein encoded by this gene is a G protein-coupled membrane receptor that binds bombesin-like peptides. This binding results in activation of a phosphatidylinositol-calcium second messenger system, with physiological effects including regulation of metabolic rate, glucose metabolism, and hypertension. [provided by RefSeq, Sep 2011]

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=0.16911522).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
BRS3	NM_001727.2	c.532T>G	p.Phe178Val	missense_variant	2/3	ENST00000370648.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
BRS3	ENST00000370648.4	c.532T>G	p.Phe178Val	missense_variant	2/3	1	NM_001727.2	P1

Frequencies

GnomAD3 genomes Cov.: 23

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 23

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

Jan 04, 2022

The c.532T>G (p.F178V) alteration is located in exon 2 (coding exon 2) of the BRS3 gene. This alteration results from a T to G substitution at nucleotide position 532, causing the phenylalanine (F) at amino acid position 178 to be replaced by a valine (V). 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	0.074
BayesDel_addAF	Benign	-0.10	T
BayesDel_noAF	Benign	-0.38
CADD	Benign	21
DANN	Uncertain	0.98
DEOGEN2	Benign	0.082	T
FATHMM_MKL	Uncertain	0.85	D
LIST_S2	Uncertain	0.92	D
M_CAP	Benign	0.037	D
MetaRNN	Benign	0.17	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.58	N
MutationTaster	Benign	0.99	D
PrimateAI	Benign	0.34	T
PROVEAN	Benign	0.37	N
REVEL	Benign	0.13
Sift	Uncertain	0.0060	D
Sift4G	Uncertain	0.030	D
Polyphen		0.010	B
Vest4		0.29
MutPred		0.60		Gain of MoRF binding (P = 0.375);
MVP		0.57
MPC		0.51
ClinPred		0.22	T
GERP RS		1.3
Varity_R		0.19
gMVP		0.67

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

No publications associated with this variant yet.

Other links and lift over

hg19: chrX-135572389;