dbSNP rs777435260: MED4:p.Asp239Asn (chr13-48077237-C-T) – ACMG Classification: Uncertain_significance (1 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2BP4

The NM_014166.4(MED4):c.715G>A(p.Asp239Asn) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000138 in 1,446,870 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: not found (cov: 32)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

MED4
NM_014166.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.65

Publications

0 publications found

Variant links:

Genes affected

MED4 (HGNC:17903): (mediator complex subunit 4) This gene encodes a component of the Mediator complex. The Mediator complex interacts with DNA-binding gene-specific transcription factors to modulate transcription by RNA polymerase II. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene. [provided by RefSeq, Jul 2012]

MED4 links:

MED4-AS1 (HGNC:39213): (MED4 antisense RNA 1)

MED4-AS1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.2930918).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014166.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
MED4	NM_014166.4	MANE Select	c.715G>A	p.Asp239Asn	missense	Exon 7 of 7	NP_054885.1	Q9NPJ6-1
MED4	NM_001270629.2		c.577G>A	p.Asp193Asn	missense	Exon 7 of 7	NP_001257558.1	Q9NPJ6-2
MED4-AS1	NR_046511.1		n.101C>T		non_coding_transcript_exon	Exon 1 of 3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
MED4	ENST00000258648.7	TSL:1 MANE Select	c.715G>A	p.Asp239Asn	missense	Exon 7 of 7	ENSP00000258648.2	Q9NPJ6-1
MED4	ENST00000963481.1		c.751G>A	p.Asp251Asn	missense	Exon 7 of 7	ENSP00000633540.1
MED4	ENST00000898190.1		c.730G>A	p.Asp244Asn	missense	Exon 7 of 7	ENSP00000568249.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000425

AC:

AN:

235022

AF XY:

0.00000785

show subpopulations

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:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000138

AC:

AN:

1446870

Hom.:

Cov.:

AF XY:

0.00000278

AC XY:

AN XY:

719660

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

32344

American (AMR)

AF:

0.00

AC:

AN:

41174

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25394

East Asian (EAS)

AF:

0.00

AC:

AN:

39016

South Asian (SAS)

AF:

0.0000239

AC:

AN:

83536

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53092

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5710

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1106772

Other (OTH)

AF:

0.00

AC:

AN:

59832

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.450

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

ExAC

AF:

0.00000824

AC:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.17

BayesDel_addAF

Benign

-0.15

BayesDel_noAF

Benign

-0.35

CADD

Uncertain

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.080

Eigen

Uncertain

0.44

Eigen_PC

Uncertain

0.55

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Uncertain

0.93

M_CAP

Benign

0.0076

MetaRNN

Benign

0.29

MetaSVM

Benign

-0.78

MutationAssessor

Benign

1.6

PhyloP100

7.7

PrimateAI

Uncertain

0.58

PROVEAN

Benign

0.24

REVEL

Benign

0.10

Sift

Benign

0.048

Sift4G

Benign

0.50

Polyphen

0.60

Vest4

0.46

MutPred

0.36

Gain of catalytic residue at P244 (P = 0.0016)

MVP

0.59

MPC

0.50

ClinPred

0.56

GERP RS

5.7

Varity_R

0.14

gMVP

0.44

Mutation Taster

=54/46

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over