rs1312659723

Variant names:

• chr14-52553154-G-A
• rs1312659723
• NM_001099652.2:c.7G>A

Your query was ambiguous. Multiple possible variants found:

• chr14-52553154-G-A
• chr14-52553154-G-T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001099652.2(GPR137C):​c.7G>A​(p.Val3Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000341 in 1,171,442 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000013 (0 hom., cov: 31)
  • Exomes 𝑓: 0.0000020 (0 hom.)
• Consequence: GPR137C NM_001099652.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.29
• Publications: 0 publications found

Genes affected

GPR137C (HGNC:25445): (G protein-coupled receptor 137C) Predicted to be involved in positive regulation of TORC1 signaling. Located in lysosomal membrane. [provided by Alliance of Genome Resources, Apr 2022]

TXNDC16 (HGNC:19965): (thioredoxin domain containing 16) Located in endoplasmic reticulum lumen. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.11911312).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001099652.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GPR137C	NM_001099652.2	MANE Select	c.7G>A	p.Val3Met	missense	Exon 1 of 7	NP_001093122.1	Q8N3F9
	GPR137C	NM_001353361.2		c.7G>A	p.Val3Met	missense	Exon 1 of 8	NP_001340290.1
	GPR137C	NR_148417.2		n.319G>A		non_coding_transcript_exon	Exon 1 of 8

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GPR137C	ENST00000321662.11	TSL:1 MANE Select	c.7G>A	p.Val3Met	missense	Exon 1 of 7	ENSP00000315106.6	Q8N3F9
	GPR137C	ENST00000866179.1		c.7G>A	p.Val3Met	missense	Exon 1 of 6	ENSP00000536238.1
	TXNDC16	ENST00000936707.1		c.-182+189C>T		intron	N/A	ENSP00000606766.1

Frequencies

GnomAD3 genomes AF: 0.0000132 AC: 2 AN: 151328 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000295

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.00000196 AC: 2 AN: 1020114 Hom.: 0 Cov.: 28 AF XY: 0.00 AC XY: 0 AN XY: 481100

African (AFR) AF: 0.00 AC: 0 AN: 20376

American (AMR) AF: 0.00 AC: 0 AN: 6476

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 11756

East Asian (EAS) AF: 0.00 AC: 0 AN: 18268

South Asian (SAS) AF: 0.00 AC: 0 AN: 18968

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 18370

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2602

European-Non Finnish (NFE) AF: 0.00000226 AC: 2 AN: 884074

Other (OTH) AF: 0.00 AC: 0 AN: 39224

GnomAD4 genome AF: 0.0000132 AC: 2 AN: 151328 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 73892

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 41344

American (AMR) AF: 0.00 AC: 0 AN: 15194

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3456

East Asian (EAS) AF: 0.00 AC: 0 AN: 5126

South Asian (SAS) AF: 0.00 AC: 0 AN: 4830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10376

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 314

European-Non Finnish (NFE) AF: 0.0000295 AC: 2 AN: 67708

Other (OTH) AF: 0.00 AC: 0 AN: 2070

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0.00233887), which strongly suggests a high chance of mosaicism in these individuals.

Alfa AF: 0.00 Hom.: 0

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.60
BayesDel_addAF	Benign	-0.17	T
BayesDel_noAF	Benign	-0.48
CADD	Uncertain	25
DANN	Uncertain	0.98
DEOGEN2	Benign	0.0019	T
Eigen	Benign	-0.22
Eigen_PC	Benign	-0.063
FATHMM_MKL	Uncertain	0.81	D
LIST_S2	Benign	0.58	T
M_CAP	Uncertain	0.15	D
MetaRNN	Benign	0.12	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.0	N
PhyloP100		3.3
PrimateAI	Pathogenic	0.93	D
PROVEAN	Benign	-0.19	N
REVEL	Benign	0.069
Sift	Benign	0.11	T
Sift4G	Benign	0.12	T
Polyphen		0.19	B
Vest4		0.31
MutPred		0.19		Loss of sheet (P = 0.0181)
MVP		0.068
MPC		1.4
ClinPred		0.45	T
GERP RS		4.1
PromoterAI		-0.0071	Neutral
Varity_R		0.077
gMVP		0.37
Mutation Taster		=95/5	polymorphism

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

Other links and lift over

dbSNP: rs1312659723; hg19: chr14-53019872;