NM_201542.5:c.*544G>A

Variant names:

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

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_201542.5(MED8):​c.*544G>A variant causes a 3 prime UTR 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_201542.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.844
• Publications: 0 publications found

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]

MED8-AS1 (HGNC:40908): (MED8 antisense RNA 1)

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.77).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_201542.5. 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
	MED8	NM_201542.5	MANE Select	c.*544G>A		3_prime_UTR	Exon 7 of 7	NP_963836.2	Q96G25-1
	MED8	NM_052877.5		c.858G>A	p.Lys286Lys	synonymous	Exon 8 of 8	NP_443109.2	Q96G25-2
	MED8	NM_001001653.3		c.*544G>A		3_prime_UTR	Exon 7 of 7	NP_001001653.1	Q96G25-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MED8	ENST00000372457.9	TSL:2 MANE Select	c.*544G>A		3_prime_UTR	Exon 7 of 7	ENSP00000361535.4	Q96G25-1
	MED8	ENST00000290663.10	TSL:5	c.858G>A	p.Lys286Lys	synonymous	Exon 8 of 8	ENSP00000290663.6	Q96G25-2
	MED8	ENST00000939322.1		c.*544G>A		3_prime_UTR	Exon 7 of 7	ENSP00000609381.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
CADD	Benign	10
DANN	Benign	0.57
PhyloP100		0.84
Mutation Taster		=100/0	polymorphism

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

Other links and lift over

dbSNP: rs372481440; hg19: chr1-43850169;