9-131860568-G-C

Variant names:

• chr9-131860568-G-C
• rs748577227
• NM_004269.4:c.906C>G

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 2P and 7B. PM2 BP4_Strong BP6_Moderate BP7

The NM_004269.4(MED27):​c.906C>G​(p.Leu302Leu) 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. Variant has been reported in ClinVar as Likely benign (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: MED27 NM_004269.4 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.205

Genes affected

MED27 (HGNC:2377): (mediator complex subunit 27) 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. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene, and a pseudogene of this gene is located on the long arm of chromosome 5. [provided by RefSeq, Dec 2011]

ACMG classification

Verdict is Likely_benign. Variant got -5 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.48).
• BP6: Variant 9-131860568-G-C is Benign according to our data. Variant chr9-131860568-G-C is described in ClinVar as [Likely_benign]. Clinvar id is 3389763.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-0.205 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MED27	NM_004269.4	c.906C>G	p.Leu302Leu	synonymous_variant	Exon 8 of 8	ENST00000292035.10	NP_004260.2
MED27	NM_001253881.2	c.798C>G	p.Leu266Leu	synonymous_variant	Exon 7 of 7		NP_001240810.1
MED27	XM_017015329.2	c.996C>G	p.Leu332Leu	synonymous_variant	Exon 9 of 9		XP_016870818.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MED27	ENST00000292035.10	c.906C>G	p.Leu302Leu	synonymous_variant	Exon 8 of 8	1	NM_004269.4	ENSP00000292035.5
MED27	ENST00000357028.6	c.798C>G	p.Leu266Leu	synonymous_variant	Exon 7 of 7	1		ENSP00000349530.3
MED27	ENST00000651950.1	c.801+2495C>G		intron_variant	Intron 7 of 8			ENSP00000498604.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000378

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Sep 01, 2024

CeGaT Center for Human Genetics Tuebingen

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

MED27: PM2:Supporting, BP4, BP7 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.48
CADD	Benign	5.6
DANN	Benign	0.73

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: rs748577227; hg19: chr9-134735955;