rs10483831

Variant names:

• chr14-70593927-C-T
• rs10483831
• NM_005466.4:c.275-549G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_005466.4(MED6):​c.275-549G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.211 in 152,070 control chromosomes in the GnomAD database, including 4,043 homozygotes. 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: 𝑓 0.21 (4043 hom., cov: 32)
• Consequence: MED6 NM_005466.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.166
• Publications: 4 publications found

Genes affected

MED6 (HGNC:19970): (mediator complex subunit 6) Enables transcription coactivator activity. Acts upstream of or within positive regulation of transcription by RNA polymerase II. Located in nucleoplasm. Part of mediator complex. [provided by Alliance of Genome Resources, Apr 2022]

DUXAP12 (HGNC:51813):

ENSG00000259115 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.303 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MED6	NM_005466.4	c.275-549G>A		intron_variant	Intron 3 of 7	ENST00000256379.10	NP_005457.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MED6	ENST00000256379.10	c.275-549G>A		intron_variant	Intron 3 of 7	1	NM_005466.4	ENSP00000256379.5

Frequencies

GnomAD3 genomes AF: 0.211 AC: 32071 AN: 151952 Hom.: 4043 Cov.: 32

Gnomad AFR AF: 0.0647

Gnomad AMI AF: 0.263

Gnomad AMR AF: 0.238

Gnomad ASJ AF: 0.335

Gnomad EAS AF: 0.283

Gnomad SAS AF: 0.316

Gnomad FIN AF: 0.239

Gnomad MID AF: 0.283

Gnomad NFE AF: 0.269

Gnomad OTH AF: 0.228

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.211 AC: 32058 AN: 152070 Hom.: 4043 Cov.: 32 AF XY: 0.213 AC XY: 15825 AN XY: 74328

African (AFR) AF: 0.0645 AC: 2680 AN: 41520

American (AMR) AF: 0.238 AC: 3635 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.335 AC: 1162 AN: 3472

East Asian (EAS) AF: 0.282 AC: 1458 AN: 5172

South Asian (SAS) AF: 0.317 AC: 1525 AN: 4816

European-Finnish (FIN) AF: 0.239 AC: 2522 AN: 10548

Middle Eastern (MID) AF: 0.277 AC: 81 AN: 292

European-Non Finnish (NFE) AF: 0.269 AC: 18276 AN: 67958

Other (OTH) AF: 0.227 AC: 479 AN: 2110

Alfa AF: 0.254 Hom.: 8921

Bravo AF: 0.201

Asia WGS AF: 0.288 AC: 998 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	3.5
DANN	Benign	0.39
PhyloP100		-0.17
Mutation Taster		=100/0	polymorphism (auto)

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: rs10483831; hg19: chr14-71060644; COSMIC: COSV56451040; COSMIC: COSV56451040;