chr5-157139389-T-C

Position:

chr5-157139389-T-C

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_004270.5(MED7):c.43A>G(p.Met15Val) variant causes a missense change. The variant allele was found at a frequency of 0.0000731 in 1,601,148 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.000072 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000073 ( 0 hom. )

Consequence

MED7
NM_004270.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.95

Variant links:

Genes affected

MED7 (HGNC:2378): (mediator complex subunit 7) The activation of gene transcription is a multistep process that is triggered by factors that recognize transcriptional enhancer sites in DNA. These factors work with co-activators to direct transcriptional initiation by the RNA polymerase II apparatus. The protein encoded by this gene is a subunit of the CRSP (cofactor required for SP1 activation) complex, which, along with TFIID, is required for efficient activation by SP1. This protein is also a component of other multisubunit complexes e.g. thyroid hormone receptor-(TR-) associated proteins which interact with TR and facilitate TR function on DNA templates in conjunction with initiation factors and cofactors. Two transcript variants encoding the same protein have been found for this gene. [provided by RefSeq, Jul 2008]

MED7 links:

HAVCR2 (HGNC:18437): (hepatitis A virus cellular receptor 2) The protein encoded by this gene belongs to the immunoglobulin superfamily, and TIM family of proteins. CD4-positive T helper lymphocytes can be divided into types 1 (Th1) and 2 (Th2) on the basis of their cytokine secretion patterns. Th1 cells are involved in cell-mediated immunity to intracellular pathogens and delayed-type hypersensitivity reactions, whereas, Th2 cells are involved in the control of extracellular helminthic infections and the promotion of atopic and allergic diseases. This protein is a Th1-specific cell surface protein that regulates macrophage activation, and inhibits Th1-mediated auto- and alloimmune responses, and promotes immunological tolerance. [provided by RefSeq, Sep 2011]

HAVCR2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.15986457).

BS2

High AC in GnomAd4 at 11 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MED7	NM_004270.5 linkuse as main transcript	c.43A>G	p.Met15Val	missense_variant	2/2	ENST00000286317.6	NP_004261.1	O43513Q6IAZ5
MED7	NM_001100816.1 linkuse as main transcript	c.43A>G	p.Met15Val	missense_variant	2/2		NP_001094286.1	O43513Q6IAZ5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
MED7	ENST00000286317.6 linkuse as main transcript	c.43A>G	p.Met15Val	missense_variant	2/2	1	NM_004270.5	ENSP00000286317.5	O43513
MED7	ENST00000420343.1 linkuse as main transcript	c.43A>G	p.Met15Val	missense_variant	2/2	2		ENSP00000401046.1	O43513
MED7	ENST00000524289.1 linkuse as main transcript	c.43A>G	p.Met15Val	missense_variant	3/3	3		ENSP00000430746.1	E5RIE8
HAVCR2	ENST00000524219.2 linkuse as main transcript	c.-294+3431A>G		intron_variant		4		ENSP00000430328.2	E5RFR4

Frequencies

GnomAD3 genomes

AF:

0.0000723

AC:

AN:

152152

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000724

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:

0.000118

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000546

AC:

AN:

238048

Hom.:

AF XY:

0.0000468

AC XY:

AN XY:

128138

show subpopulations

Gnomad AFR exome

AF:

0.000124

Gnomad AMR exome

AF:

0.0000604

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000740

Gnomad OTH exome

AF:

0.000173

GnomAD4 exome

AF:

0.0000732

AC:

106

AN:

1448996

Hom.:

Cov.:

AF XY:

0.0000708

AC XY:

AN XY:

720020

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000695

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000479

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000850

Gnomad4 OTH exome

AF:

0.0000835

GnomAD4 genome

AF:

0.0000723

AC:

AN:

152152

Hom.:

Cov.:

AF XY:

0.0000538

AC XY:

AN XY:

74332

show subpopulations

Gnomad4 AFR

AF:

0.0000724

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000118

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000167

Hom.:

Bravo

AF:

0.0000718

ESP6500AA

AF:

0.000227

AC:

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.0000330

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jul 07, 2024

The c.43A>G (p.M15V) alteration is located in exon 2 (coding exon 1) of the MED7 gene. This alteration results from a A to G substitution at nucleotide position 43, causing the methionine (M) at amino acid position 15 to be replaced by a valine (V). 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

0.083

BayesDel_addAF

Benign

-0.050

BayesDel_noAF

Uncertain

0.0

CADD

Benign

DANN

Benign

0.92

DEOGEN2

Benign

0.091

T;T;T

Eigen

Benign

-0.20

Eigen_PC

Benign

0.033

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Uncertain

0.96

D;.;D

M_CAP

Benign

0.0022

MetaRNN

Benign

0.16

T;T;T

MetaSVM

Benign

-0.98

MutationAssessor

Benign

0.95

L;L;.

PrimateAI

Uncertain

0.75

PROVEAN

Benign

-1.3

N;N;N

REVEL

Benign

0.16

Sift

Benign

0.75

T;T;T

Sift4G

Benign

0.93

T;T;.

Polyphen

0.036

B;B;.

Vest4

0.45

MVP

0.44

MPC

0.44

ClinPred

0.064

GERP RS

5.6

Varity_R

0.22

gMVP

0.63

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over