rs750049200

Variant names:

• chr17-6650063-C-A
• rs750049200
• NM_016060.3:c.122G>T

Your query was ambiguous. Multiple possible variants found:

• chr17-6650063-C-A
• chr17-6650063-C-T

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_016060.3(MED31):​c.122G>T​(p.Gly41Val) variant causes a missense change. The variant allele was found at a frequency of 0.0000119 in 1,595,494 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000033 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0000097 (0 hom.)
• Consequence: MED31 NM_016060.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.65
• Publications: 1 publications found

Genes affected

MED31 (HGNC:24260): (mediator complex subunit 31) Predicted to enable transcription coregulator activity and ubiquitin protein ligase activity. Predicted to be involved in regulation of transcription by RNA polymerase II. Predicted to act upstream of or within limb development and negative regulation of fibroblast proliferation. Predicted to be located in nucleoplasm. Predicted to be part of core mediator complex and mediator complex. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Uncertain_significance. The variant received 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.882

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_016060.3. 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
	MED31	NM_016060.3	MANE Select	c.122G>T	p.Gly41Val	missense	Exon 3 of 4	NP_057144.1	Q9Y3C7

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MED31	ENST00000225728.8	TSL:1 MANE Select	c.122G>T	p.Gly41Val	missense	Exon 3 of 4	ENSP00000225728.3	Q9Y3C7
	MED31	ENST00000574128.1	TSL:3	c.-101G>T		5_prime_UTR	Exon 3 of 4	ENSP00000459723.1	I3L2J1
	MED31	ENST00000575197.1	TSL:2	c.106+293G>T		intron	N/A	ENSP00000458248.1	I3L0P8

Frequencies

GnomAD3 genomes AF: 0.0000329 AC: 5 AN: 151972 Hom.: 0 Cov.: 32

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: 0.0000735

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.00000867 AC: 2 AN: 230596 AF XY: 0.00000800

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000186

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000970 AC: 14 AN: 1443522 Hom.: 0 Cov.: 30 AF XY: 0.00000836 AC XY: 6 AN XY: 717522

African (AFR) AF: 0.00 AC: 0 AN: 31984

American (AMR) AF: 0.00 AC: 0 AN: 39544

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25388

East Asian (EAS) AF: 0.00 AC: 0 AN: 39538

South Asian (SAS) AF: 0.00 AC: 0 AN: 81226

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53224

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5664

European-Non Finnish (NFE) AF: 0.0000126 AC: 14 AN: 1107376

Other (OTH) AF: 0.00 AC: 0 AN: 59578

GnomAD4 genome AF: 0.0000329 AC: 5 AN: 151972 Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1 AN XY: 74222

African (AFR) AF: 0.00 AC: 0 AN: 41362

American (AMR) AF: 0.00 AC: 0 AN: 15264

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 5194

South Asian (SAS) AF: 0.00 AC: 0 AN: 4820

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10564

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000735 AC: 5 AN: 67986

Other (OTH) AF: 0.00 AC: 0 AN: 2082

Alfa AF: 0.0000329 Hom.: 0

Bravo AF: 0.0000340

ExAC AF: 0.00000824 AC: 1

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	0.98
BayesDel_addAF	Pathogenic	0.45	D
BayesDel_noAF	Pathogenic	0.41
CADD	Pathogenic	32
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.67	D
Eigen	Pathogenic	0.92
Eigen_PC	Pathogenic	0.86
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Pathogenic	0.98	D
M_CAP	Benign	0.051	D
MetaRNN	Pathogenic	0.88	D
MetaSVM	Uncertain	0.32	D
MutationAssessor	Pathogenic	3.6	H
PhyloP100		5.6
PrimateAI	Pathogenic	0.85	D
PROVEAN	Pathogenic	-8.6	D
REVEL	Pathogenic	0.70
Sift	Uncertain	0.014	D
Sift4G	Uncertain	0.018	D
Polyphen		1.0	D
Vest4		0.87
MutPred		0.61		Gain of ubiquitination at K46 (P = 0.0882)
MVP		0.85
MPC		1.8
ClinPred		1.0	D
GERP RS		5.6
Varity_R		0.87
gMVP		0.79
Mutation Taster		=192/108	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs750049200; hg19: chr17-6553383;