NM_004831.5:c.1327G>C

Variant names:

• chr19-16576503-C-G
• rs2086001419
• NM_004831.5:c.1327G>C

Variant summary

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

The NM_004831.5(MED26):​c.1327G>C​(p.Val443Leu) variant causes a missense 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. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: MED26 NM_004831.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.912
• Publications: 0 publications found

Genes affected

MED26 (HGNC:2376): (mediator complex subunit 26) 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]

ENSG00000141979 (HGNC:):

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 (MetaRNN=0.03137043).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004831.5. 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
	MED26	NM_004831.5	MANE Select	c.1327G>C	p.Val443Leu	missense	Exon 3 of 3	NP_004822.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MED26	ENST00000263390.8	TSL:1 MANE Select	c.1327G>C	p.Val443Leu	missense	Exon 3 of 3	ENSP00000263390.3	O95402-1
	MED26	ENST00000611692.4	TSL:1	c.*692G>C		3_prime_UTR	Exon 4 of 4	ENSP00000484490.1	O95402-2
	ENSG00000141979	ENST00000409035.1	TSL:2	n.1211+140G>C		intron	N/A	ENSP00000386951.2	B8ZZF3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

Alfa AF: 0.0000312 Hom.: 0

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.094
BayesDel_addAF	Benign	-0.28	T
BayesDel_noAF	Benign	-0.64
CADD	Benign	14
DANN	Benign	0.91
DEOGEN2	Benign	0.040	T
Eigen	Benign	-0.61
Eigen_PC	Benign	-0.49
FATHMM_MKL	Benign	0.20	N
LIST_S2	Benign	0.57	T
M_CAP	Benign	0.0024	T
MetaRNN	Benign	0.031	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.0	L
PhyloP100		0.91
PrimateAI	Benign	0.38	T
PROVEAN	Benign	0.19	N
REVEL	Benign	0.047
Sift	Benign	0.39	T
Sift4G	Benign	0.74	T
Polyphen		0.0	B
Vest4		0.039
MutPred		0.085		Loss of MoRF binding (P = 0.1163)
MVP		0.15
MPC		0.30
ClinPred		0.039	T
GERP RS		1.6
Varity_R		0.059
gMVP		0.041
Mutation Taster		=91/9	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: rs2086001419; hg19: chr19-16687314;