3-170084342-T-C

Variant names:

• chr3-170084342-T-C
• NM_014373.3:c.370T>C

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_014373.3(GPR160):​c.370T>C​(p.Phe124Leu) 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. 14/21 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: GPR160 NM_014373.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.269

Genes affected

GPR160 (HGNC:23693): (G protein-coupled receptor 160) Predicted to enable G protein-coupled receptor activity. Predicted to be involved in G protein-coupled receptor signaling pathway. Located in plasma membrane. Part of receptor complex. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

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=0.031265527).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GPR160	NM_014373.3	c.370T>C	p.Phe124Leu	missense_variant	Exon 4 of 4	ENST00000355897.10	NP_055188.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GPR160	ENST00000355897.10	c.370T>C	p.Phe124Leu	missense_variant	Exon 4 of 4	1	NM_014373.3	ENSP00000348161.5
GPR160	ENST00000485735.6	c.370T>C	p.Phe124Leu	missense_variant	Exon 3 of 3	2		ENSP00000419546.2
GPR160	ENST00000473675.1	c.370T>C	p.Phe124Leu	missense_variant	Exon 3 of 3	3		ENSP00000420751.1
GPR160	ENST00000482710.1	c.*105T>C		downstream_gene_variant		2		ENSP00000419400.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 29

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

May 04, 2022

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.370T>C (p.F124L) alteration is located in exon 4 (coding exon 1) of the GPR160 gene. This alteration results from a T to C substitution at nucleotide position 370, causing the phenylalanine (F) at amino acid position 124 to be replaced by a leucine (L). 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	0.36
BayesDel_addAF	Benign	-0.19	T
BayesDel_noAF	Benign	-0.51
CADD	Benign	16
DANN	Benign	0.69
DEOGEN2	Benign	0.0038	T;.;.
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.084	N
LIST_S2	Benign	0.44	T;T;T
M_CAP	Benign	0.0064	T
MetaRNN	Benign	0.031	T;T;T
MetaSVM	Benign	-0.97	T
MutationAssessor	Benign	1.6	L;.;.
PrimateAI	Benign	0.34	T
PROVEAN	Benign	-0.79	N;N;N
REVEL	Benign	0.052
Sift	Benign	0.60	T;T;T
Sift4G	Benign	0.53	T;T;T
Polyphen		0.0050	B;.;.
Vest4		0.026
MutPred		0.23		Gain of helix (P = 0.0854);Gain of helix (P = 0.0854);Gain of helix (P = 0.0854);
MVP		0.014
MPC		0.11
ClinPred		0.044	T
GERP RS		0.35
Varity_R		0.028
gMVP		0.17

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: chr3-169802130;