3-170084978-A-C

Variant names:

• chr3-170084978-A-C
• NM_014373.3:c.1006A>C

Variant summary

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

The NM_014373.3(GPR160):​c.1006A>C​(p.Met336Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000758 in 1,319,694 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/20 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)
  • Exomes 𝑓: 7.6e-7 (0 hom.)
• Consequence: GPR160 NM_014373.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.48

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 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=0.09027398).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GPR160	NM_014373.3	c.1006A>C	p.Met336Leu	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.1006A>C	p.Met336Leu	missense_variant	Exon 4 of 4	1	NM_014373.3	ENSP00000348161.5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 7.58e-7 AC: 1 AN: 1319694 Hom.: 0 Cov.: 21 AF XY: 0.00 AC XY: 0 AN XY: 656746

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: 9.80e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Nov 21, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.1006A>C (p.M336L) alteration is located in exon 4 (coding exon 1) of the GPR160 gene. This alteration results from a A to C substitution at nucleotide position 1006, causing the methionine (M) at amino acid position 336 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	Benign	0.085
BayesDel_addAF	Benign	-0.18	T
BayesDel_noAF	Benign	-0.50
CADD	Benign	14
DANN	Benign	0.65
DEOGEN2	Benign	0.019	T
Eigen	Benign	-0.78
Eigen_PC	Benign	-0.67
FATHMM_MKL	Uncertain	0.97	D
LIST_S2	Benign	0.42	T
M_CAP	Benign	0.0017	T
MetaRNN	Benign	0.090	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.0	N
PrimateAI	Benign	0.42	T
PROVEAN	Benign	0.46	N
REVEL	Benign	0.063
Sift	Benign	0.037	D
Sift4G	Benign	0.071	T
Polyphen		0.0010	B
Vest4		0.28
MutPred		0.33		Loss of disorder (P = 0.0587);
MVP		0.014
MPC		0.083
ClinPred		0.11	T
GERP RS		3.4
Varity_R		0.086
gMVP		0.39

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: chr3-169802766;