rs748577227

Variant names:

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

Your query was ambiguous. Multiple possible variants found:

• chr9-131860568-G-A
• chr9-131860568-G-C

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 0P and 3B. BP4_Moderate BP7

The NM_004269.4(MED27):​c.906C>T​(p.Leu302Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000169 in 1,423,406 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. L302L) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.000017 (0 hom.)
• Consequence: MED27 NM_004269.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.205
• Publications: 0 publications found

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]

MED27 Gene-Disease associations (from GenCC):

• neurodevelopmental disorder with spasticity, cataracts, and cerebellar hypoplasia

  Inheritance: AR Classification: STRONG Submitted by: ClinGen, G2P, Labcorp Genetics (formerly Invitae)
• syndromic intellectual disability

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Likely_benign. The variant received -3 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.44).
• 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>T	p.Leu302Leu	synonymous_variant	Exon 8 of 8	ENST00000292035.10	NP_004260.2
MED27	NM_001253881.2	c.798C>T	p.Leu266Leu	synonymous_variant	Exon 7 of 7		NP_001240810.1
MED27	XM_017015329.2	c.996C>T	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>T	p.Leu302Leu	synonymous_variant	Exon 8 of 8	1	NM_004269.4	ENSP00000292035.5
MED27	ENST00000357028.6	c.798C>T	p.Leu266Leu	synonymous_variant	Exon 7 of 7	1		ENSP00000349530.3
MED27	ENST00000651950.1	c.801+2495C>T		intron_variant	Intron 7 of 8			ENSP00000498604.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.0000202 AC: 4 AN: 197914 AF XY: 0.0000188

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000236

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000169 AC: 24 AN: 1423406 Hom.: 0 Cov.: 31 AF XY: 0.0000170 AC XY: 12 AN XY: 704852

African (AFR) AF: 0.00 AC: 0 AN: 32506

American (AMR) AF: 0.00 AC: 0 AN: 39946

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24908

East Asian (EAS) AF: 0.00 AC: 0 AN: 38178

South Asian (SAS) AF: 0.0000617 AC: 5 AN: 81022

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 50902

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4620

European-Non Finnish (NFE) AF: 0.0000165 AC: 18 AN: 1092568

Other (OTH) AF: 0.0000170 AC: 1 AN: 58756

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.44
CADD	Benign	8.8
DANN	Benign	0.83
PhyloP100		-0.20

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: rs748577227; hg19: chr9-134735955;