Variant 19-868936-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_005481.3(MED16):c.2326C>A(p.Gln776Lys) variant causes a missense change. The variant allele was found at a frequency of 0.00000216 in 1,389,090 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000022 ( 0 hom. )

Consequence

MED16
NM_005481.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.27

Variant links:

Genes affected

MED16 (HGNC:17556): (mediator complex subunit 16) Enables thyroid hormone receptor binding activity and transcription coactivator activity. Involved in positive regulation of transcription initiation from RNA polymerase II promoter. Located in membrane. Part of mediator complex. [provided by Alliance of Genome Resources, Apr 2022]

MED16 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.2545766).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MED16	NM_005481.3 linkuse as main transcript	c.2326C>A	p.Gln776Lys	missense_variant	14/16	ENST00000325464.6	NP_005472.2	Q9Y2X0-1
MED16	XM_017026120.3 linkuse as main transcript	c.2119C>A	p.Gln707Lys	missense_variant	13/15		XP_016881609.1
MED16	XM_047438010.1 linkuse as main transcript	c.2119C>A	p.Gln707Lys	missense_variant	13/14		XP_047293966.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MED16	ENST00000325464.6 linkuse as main transcript	c.2326C>A	p.Gln776Lys	missense_variant	14/16	5	NM_005481.3	ENSP00000325612.1		Q9Y2X0-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000216

AC:

AN:

1389090

Hom.:

Cov.:

AF XY:

0.00000291

AC XY:

AN XY:

686830

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.0000263

Gnomad4 NFE exome

AF:

0.00000185

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Aug 08, 2022

The c.2326C>A (p.Q776K) alteration is located in exon 14 (coding exon 13) of the MED16 gene. This alteration results from a C to A substitution at nucleotide position 2326, causing the glutamine (Q) at amino acid position 776 to be replaced by a lysine (K). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.16

BayesDel_addAF

Benign

-0.072

BayesDel_noAF

Benign

-0.34

CADD

Uncertain

DANN

Uncertain

0.99

DEOGEN2

Benign

0.052

.;.;T;T

Eigen

Benign

0.015

Eigen_PC

Benign

0.15

FATHMM_MKL

Uncertain

0.97

LIST_S2

Uncertain

0.89

D;D;.;D

M_CAP

Benign

0.013

MetaRNN

Benign

0.25

T;T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.4

L;.;L;L

MutationTaster

Benign

0.97

D;D;D;D;D

PrimateAI

Uncertain

0.67

PROVEAN

Benign

-1.1

N;N;.;N

REVEL

Benign

0.043

Sift

Benign

0.039

D;D;.;D

Sift4G

Uncertain

0.056

T;T;D;D

Polyphen

0.34, 0.39

.;B;B;B

Vest4

0.54

MutPred

0.29

Gain of catalytic residue at Q776 (P = 0.0032);.;Gain of catalytic residue at Q776 (P = 0.0032);Gain of catalytic residue at Q776 (P = 0.0032);

MVP

0.30

ClinPred

0.74

GERP RS

4.7

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

Varity_R

0.28

gMVP

0.30

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over