1-43384498-C-T

Variant names:

• chr1-43384498-C-T
• rs372481440
• NM_201542.5:c.*544G>A

Variant summary

Our verdict is Likely benign. Variant got -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP7

The NM_052877.5(MED8):​c.858G>A​(p.Lys286Lys) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: MED8 NM_052877.5 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.844

Genes affected

MED8 (HGNC:19971): (mediator complex subunit 8) This gene encodes a protein component of the mediator complex, which aids in transcriptional activation through interaction with RNA polymerase II and gene-specific transcription factors. The encoded protein may also function in ubiquitin ligation and protein degradation. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene. [provided by RefSeq, Jan 2013]

ACMG classification

Verdict is Likely_benign. Variant got -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.77).
• BP7: Synonymous conserved (PhyloP=0.844 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MED8	NM_201542.5	c.*544G>A		3_prime_UTR_variant	Exon 7 of 7	ENST00000372457.9	NP_963836.2
MED8	NM_052877.5	c.858G>A	p.Lys286Lys	synonymous_variant	Exon 8 of 8		NP_443109.2
MED8	NM_001001653.3	c.*544G>A		3_prime_UTR_variant	Exon 7 of 7		NP_001001653.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MED8	ENST00000372457	c.*544G>A		3_prime_UTR_variant	Exon 7 of 7	2	NM_201542.5	ENSP00000361535.4
MED8	ENST00000290663.10	c.858G>A	p.Lys286Lys	synonymous_variant	Exon 8 of 8	5		ENSP00000290663.6
MED8	ENST00000372455.4	c.*544G>A		downstream_gene_variant		1		ENSP00000361533.4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
CADD	Benign	10
DANN	Benign	0.57

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

Other links and lift over

dbSNP: rs372481440; hg19: chr1-43850169;