rs36120755

chr11-93797651-A-G

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_004268.5(MED17):c.1260A>G(p.Ser420=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00615 in 1,613,904 control chromosomes in the GnomAD database, including 531 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.033 (281 hom., cov: 32)
  • Exomes 𝑓: 0.0033 (250 hom.)
• Consequence: MED17 NM_004268.5 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: 0.120

Genes affected

MED17 (HGNC:2375): (mediator complex subunit 17) The activation of gene transcription is a multistep process that is triggered by factors that recognize transcriptional enhancer sites in DNA. These factors work with co-activators to direct transcriptional initiation by the RNA polymerase II apparatus. The protein encoded by this gene is a subunit of the CRSP (cofactor required for SP1 activation) complex, which, along with TFIID, is required for efficient activation by SP1. This protein is also a component of other multisubunit complexes e.g. thyroid hormone receptor-(TR-) associated proteins which interact with TR and facilitate TR function on DNA templates in conjunction with initiation factors and cofactors. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.75).
• BP6: Variant 11-93797651-A-G is Benign according to our data. Variant chr11-93797651-A-G is described in ClinVar as [Benign]. Clinvar id is 129598.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-93797651-A-G is described in Lovd as [Benign].
• BP7: Synonymous conserved (PhyloP=0.12 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.114 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MED17	NM_004268.5	c.1260A>G	p.Ser420=	synonymous_variant	8/12	ENST00000251871.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MED17	ENST00000251871.9	c.1260A>G	p.Ser420=	synonymous_variant	8/12	1	NM_004268.5	P1

Frequencies

GnomAD3 genomes AF: 0.0333 AC: 5071 AN: 152172 Hom.: 280 Cov.: 32

Gnomad AFR AF: 0.117

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0110

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000828

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.000338

Gnomad OTH AF: 0.0215

GnomAD3 exomes AF: 0.00832 AC: 2090 AN: 251266 Hom.: 110 AF XY: 0.00604 AC XY: 821 AN XY: 135822

Gnomad AFR exome AF: 0.115

Gnomad AMR exome AF: 0.00463

Gnomad ASJ exome AF: 0.0000992

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000196

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000273

Gnomad OTH exome AF: 0.00343

GnomAD4 exome AF: 0.00331 AC: 4832 AN: 1461616 Hom.: 250 Cov.: 30 AF XY: 0.00277 AC XY: 2016 AN XY: 727112

Gnomad4 AFR exome AF: 0.117

Gnomad4 AMR exome AF: 0.00503

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000325

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000152

Gnomad4 OTH exome AF: 0.00762

GnomAD4 genome AF: 0.0334 AC: 5091 AN: 152288 Hom.: 281 Cov.: 32 AF XY: 0.0324 AC XY: 2410 AN XY: 74472

Gnomad4 AFR AF: 0.117

Gnomad4 AMR AF: 0.0110

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000829

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000338

Gnomad4 OTH AF: 0.0213

Alfa AF: 0.0175 Hom.: 67

Bravo AF: 0.0378

Asia WGS AF: 0.00433 AC: 15 AN: 3478

EpiCase AF: 0.000327

EpiControl AF: 0.000296

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Jul 31, 2018	- -
Benign, criteria provided, single submitter	clinical testing	Invitae	Jan 31, 2024	- -

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

Genetic Services Laboratory, University of Chicago

Jan 10, 2013

- -

Infantile cerebral and cerebellar atrophy with postnatal progressive microcephaly Benign:1

Benign, no assertion criteria provided

clinical testing

Natera, Inc.

Sep 16, 2020

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.75
Cadd	Benign	6.0
Dann	Benign	0.76

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: rs36120755; hg19: chr11-93530817;