3-151199344-C-T

Variant names:

• chr3-151199344-C-T
• NM_013308.4:c.43G>A

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_013308.4(GPR171):​c.43G>A​(p.Glu15Lys) 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. 15/21 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: GPR171 NM_013308.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.15

Genes affected

GPR171 (HGNC:30057): (G protein-coupled receptor 171) Predicted to enable G protein-coupled purinergic nucleotide receptor activity. Predicted to be involved in G protein-coupled receptor signaling pathway. Predicted to act upstream of or within negative regulation of myeloid cell differentiation. Predicted to be located in plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

MED12L (HGNC:16050): (mediator complex subunit 12L) The protein encoded by this gene is part of the Mediator complex, which is involved in transcriptional coactivation of nearly all RNA polymerase II-dependent genes. The Mediator complex links gene-specific transcriptional activators with the basal transcription machinery. [provided by RefSeq, May 2010]

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.3888675).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GPR171	NM_013308.4	c.43G>A	p.Glu15Lys	missense_variant	Exon 3 of 3	ENST00000309180.6	NP_037440.3
MED12L	NM_001393769.1	c.2250+5678C>T		intron_variant	Intron 16 of 44	ENST00000687756.1	NP_001380698.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GPR171	ENST00000309180.6	c.43G>A	p.Glu15Lys	missense_variant	Exon 3 of 3	1	NM_013308.4	ENSP00000308479.5
MED12L	ENST00000687756.1	c.2250+5678C>T		intron_variant	Intron 16 of 44		NM_001393769.1	ENSP00000508695.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

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 20, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.43G>A (p.E15K) alteration is located in exon 3 (coding exon 1) of the GPR171 gene. This alteration results from a G to A substitution at nucleotide position 43, causing the glutamic acid (E) at amino acid position 15 to be replaced by a lysine (K). 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	0.0053	T
BayesDel_noAF	Benign	-0.23
CADD	Benign	16
DANN	Benign	0.91
DEOGEN2	Benign	0.0036	T;T;.
Eigen	Benign	0.13
Eigen_PC	Benign	0.20
FATHMM_MKL	Uncertain	0.84	D
LIST_S2	Benign	0.83	.;T;.
M_CAP	Benign	0.011	T
MetaRNN	Benign	0.39	T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.0	L;L;.
PrimateAI	Benign	0.46	T
PROVEAN	Benign	0.32	N;.;D
REVEL	Benign	0.16
Sift	Benign	0.77	T;.;.
Sift4G	Benign	0.44	T;T;.
Polyphen		0.95	P;P;.
Vest4		0.35
MutPred		0.62		Gain of methylation at E15 (P = 0.0206);Gain of methylation at E15 (P = 0.0206);Gain of methylation at E15 (P = 0.0206);
MVP		0.54
MPC		0.27
ClinPred		0.39	T
GERP RS		5.5
Varity_R		0.12
gMVP		0.45

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.080		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: chr3-150917131;