rs1338147934

Variant names:

• chrX-40682702-G-A
• NM_004229.4:c.2266C>T

Your query was ambiguous. Multiple possible variants found:

• chrX-40682702-G-A
• chrX-40682702-G-T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_004229.4(MED14):​c.2266C>T​(p.Pro756Ser) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000914 in 1,094,127 control chromosomes in the GnomAD database, with no homozygous occurrence. There are no hemizygote samples in GnomAD. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P756T) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 22)
  • Exomes 𝑓: 9.1e-7 (0 hom. 0 hem.)
• Consequence: MED14 NM_004229.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 9.60

Genes affected

MED14 (HGNC:2370): (mediator complex subunit 14) 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. This protein contains a bipartite nuclear localization signal. This gene is known to escape chromosome X-inactivation. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MED14	NM_004229.4	c.2266C>T	p.Pro756Ser	missense_variant	Exon 18 of 31	ENST00000324817.6	NP_004220.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MED14	ENST00000324817.6	c.2266C>T	p.Pro756Ser	missense_variant	Exon 18 of 31	1	NM_004229.4	ENSP00000323720.1
MED14	ENST00000496531.2	n.126C>T		non_coding_transcript_exon_variant	Exon 2 of 5	5

Frequencies

GnomAD3 genomes Cov.: 22

GnomAD4 exome AF: 9.14e-7 AC: 1 AN: 1094127 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 359725

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000332

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 22

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.62
BayesDel_addAF	Pathogenic	0.25	D
BayesDel_noAF	Uncertain	0.13
CADD	Uncertain	23
DANN	Benign	0.94
DEOGEN2	Benign	0.086	T
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Pathogenic	0.99	D
M_CAP	Uncertain	0.20	D
MetaRNN	Uncertain	0.67	D
MetaSVM	Benign	-0.81	T
MutationAssessor	Benign	0.81	L
PrimateAI	Uncertain	0.77	T
PROVEAN	Benign	0.52	N
REVEL	Benign	0.26
Sift	Benign	0.61	T
Sift4G	Benign	0.37	T
Polyphen		0.99	D
Vest4		0.70
MutPred		0.26		Gain of helix (P = 0.027);
MVP		0.85
MPC		1.0
ClinPred		0.66	D
GERP RS		5.8
Varity_R		0.21
gMVP		0.64

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

No publications associated with this variant yet.

Other links and lift over

hg19: chrX-40541954;