NM_004831.5:c.1322A>T

Variant names:

• chr19-16576508-T-A
• NM_004831.5:c.1322A>T

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_004831.5(MED26):​c.1322A>T​(p.Glu441Val) variant causes a missense change. 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 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: 5.71
• 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: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.27156705).

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.1322A>T	p.Glu441Val	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.1322A>T	p.Glu441Val	missense	Exon 3 of 3	ENSP00000263390.3	O95402-1
	MED26	ENST00000611692.4	TSL:1	c.*687A>T		3_prime_UTR	Exon 4 of 4	ENSP00000484490.1	O95402-2
	ENSG00000141979	ENST00000409035.1	TSL:2	n.1211+135A>T		intron	N/A	ENSP00000386951.2	B8ZZF3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

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	0.32
BayesDel_addAF	Benign	-0.055	T
BayesDel_noAF	Benign	-0.32
CADD	Uncertain	25
DANN	Uncertain	0.99
DEOGEN2	Benign	0.15	T
Eigen	Uncertain	0.60
Eigen_PC	Uncertain	0.60
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Benign	0.79	T
M_CAP	Benign	0.036	D
MetaRNN	Benign	0.27	T
MetaSVM	Benign	-0.66	T
MutationAssessor	Uncertain	2.3	M
PhyloP100		5.7
PrimateAI	Benign	0.41	T
PROVEAN	Uncertain	-2.4	N
REVEL	Benign	0.10
Sift	Uncertain	0.0010	D
Sift4G	Uncertain	0.0050	D
Polyphen		0.99	D
Vest4		0.20
MutPred		0.23		Gain of MoRF binding (P = 0.0141)
MVP		0.34
MPC		0.90
ClinPred		0.96	D
GERP RS		5.1
Varity_R		0.26
gMVP		0.23
Mutation Taster		=65/35	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

hg19: chr19-16687319;