chr3-151198652-C-T

Variant names:

• chr3-151198652-C-T
• rs80187285
• NM_013308.4:c.735G>A

Variant summary

Our verdict is Benign. The variant received -7 ACMG points: 0P and 7B. BP4_Strong BP6_Moderate BP7

The NM_013308.4(GPR171):​c.735G>A​(p.Pro245Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00139 in 1,613,936 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.00097 (1 hom., cov: 32)
  • Exomes 𝑓: 0.0014 (1 hom.)
• Consequence: GPR171 NM_013308.4 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.415
• Publications: 3 publications found

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]

MED12L Gene-Disease associations (from GenCC):

• Nizon-Isidor syndrome

  Inheritance: AD Classification: DEFINITIVE, STRONG, MODERATE Submitted by: Ambry Genetics, ClinGen, Illumina, Labcorp Genetics (formerly Invitae)
• autosomal dominant non-syndromic intellectual disability

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -7 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.47).
• BP6: Variant 3-151198652-C-T is Benign according to our data. Variant chr3-151198652-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 2672965.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-0.415 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_013308.4. 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
	GPR171	NM_013308.4	MANE Select	c.735G>A	p.Pro245Pro	synonymous	Exon 3 of 3	NP_037440.3
	MED12L	NM_001393769.1	MANE Select	c.2250+4986C>T		intron	N/A	NP_001380698.1	A0A8I5KX78
	MED12L	NM_053002.6		c.2145+4986C>T		intron	N/A	NP_443728.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GPR171	ENST00000309180.6	TSL:1 MANE Select	c.735G>A	p.Pro245Pro	synonymous	Exon 3 of 3	ENSP00000308479.5	O14626
	MED12L	ENST00000687756.1	MANE Select	c.2250+4986C>T		intron	N/A	ENSP00000508695.1	A0A8I5KX78
	MED12L	ENST00000474524.5	TSL:1	c.2145+4986C>T		intron	N/A	ENSP00000417235.1	Q86YW9-1

Frequencies

GnomAD3 genomes AF: 0.000973 AC: 148 AN: 152054 Hom.: 1 Cov.: 32

Gnomad AFR AF: 0.000193

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000917

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000192

Gnomad SAS AF: 0.000622

Gnomad FIN AF: 0.000189

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00172

Gnomad OTH AF: 0.00144

GnomAD2 exomes AF: 0.000708 AC: 178 AN: 251400 AF XY: 0.000721

Gnomad AFR exome AF: 0.0000615

Gnomad AMR exome AF: 0.000838

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00114

Gnomad OTH exome AF: 0.00114

GnomAD4 exome AF: 0.00143 AC: 2091 AN: 1461764 Hom.: 1 Cov.: 32 AF XY: 0.00137 AC XY: 997 AN XY: 727182

African (AFR) AF: 0.000179 AC: 6 AN: 33480

American (AMR) AF: 0.000939 AC: 42 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39698

South Asian (SAS) AF: 0.000267 AC: 23 AN: 86256

European-Finnish (FIN) AF: 0.0000749 AC: 4 AN: 53416

Middle Eastern (MID) AF: 0.000173 AC: 1 AN: 5768

European-Non Finnish (NFE) AF: 0.00174 AC: 1934 AN: 1111894

Other (OTH) AF: 0.00132 AC: 80 AN: 60392

GnomAD4 genome AF: 0.000973 AC: 148 AN: 152172 Hom.: 1 Cov.: 32 AF XY: 0.000833 AC XY: 62 AN XY: 74408

African (AFR) AF: 0.000193 AC: 8 AN: 41518

American (AMR) AF: 0.000916 AC: 14 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5184

South Asian (SAS) AF: 0.000623 AC: 3 AN: 4818

European-Finnish (FIN) AF: 0.000189 AC: 2 AN: 10586

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00172 AC: 117 AN: 68002

Other (OTH) AF: 0.00143 AC: 3 AN: 2102

Alfa AF: 0.00111 Hom.: 0

Bravo AF: 0.000918

Asia WGS AF: 0.000866 AC: 3 AN: 3478

EpiCase AF: 0.00131

EpiControl AF: 0.00113

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.47
CADD	Benign	7.1
DANN	Benign	0.74
PhyloP100		-0.41
Mutation Taster		=98/2	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: rs80187285; hg19: chr3-150916439; COSMIC: COSV56384508; COSMIC: COSV56384508;