rs144767798

Variant names:

• chr9-133341534-C-A
• NM_133640.5:c.574G>T

Your query was ambiguous. Multiple possible variants found:

• chr9-133341534-C-A
• chr9-133341534-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_133640.5(MED22):​c.574G>T​(p.Gly192Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000724 in 1,380,734 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G192S) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 7.2e-7 (0 hom.)
• Consequence: MED22 NM_133640.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.171

Genes affected

MED22 (HGNC:11477): (mediator complex subunit 22) This gene encodes a protein component of the mediator complex, which functions in the regulation of transcription by bridging interactions between gene-specific regulatory factors, RNA polymerase II, and general transcription factors. Alternatively spliced transcript variants encoding different isoforms have been observed. [provided by RefSeq, Jul 2013]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.09118).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MED22	NM_133640.5	c.574G>T	p.Gly192Cys	missense_variant	Exon 5 of 5	ENST00000343730.10	NP_598395.1
MED22	NM_181491.3	c.*2581G>T		3_prime_UTR_variant	Exon 4 of 4		NP_852468.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MED22	ENST00000343730.10	c.574G>T	p.Gly192Cys	missense_variant	Exon 5 of 5	1	NM_133640.5	ENSP00000342343.5
MED22	ENST00000610888	c.*2581G>T		3_prime_UTR_variant	Exon 4 of 4	1		ENSP00000478773.1
MED22	ENST00000614493	c.*2581G>T		3_prime_UTR_variant	Exon 4 of 4	2		ENSP00000481493.1
MED22	ENST00000610672.4	c.574G>T	p.Gly192Cys	missense_variant	Exon 5 of 5	2		ENSP00000482438.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 7.24e-7 AC: 1 AN: 1380734 Hom.: 0 Cov.: 29 AF XY: 0.00000146 AC XY: 1 AN XY: 684444

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000137

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.084
BayesDel_addAF	Benign	-0.12	T
BayesDel_noAF	Benign	-0.42
CADD	Benign	12
DANN	Benign	0.95
DEOGEN2	Benign	0.018	T;T
Eigen	Benign	-1.0
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.18	N
LIST_S2	Benign	0.61	.;T
M_CAP	Benign	0.030	D
MetaRNN	Benign	0.091	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.0	N;N
PrimateAI	Benign	0.45	T
PROVEAN	Benign	-0.64	.;N
REVEL	Benign	0.074
Sift	Uncertain	0.013	.;D
Sift4G	Uncertain	0.011	D;D
Polyphen		0.58	P;P
Vest4		0.14
MutPred		0.15		Gain of loop (P = 0.0435);Gain of loop (P = 0.0435);
MVP		0.23
ClinPred		0.13	T
GERP RS		-1.6
Varity_R		0.099
gMVP		0.24

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr9-136208384;