Variant 19-868897-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_005481.3(MED16):c.2365G>A(p.Ala789Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000468 in 1,551,506 control chromosomes in the GnomAD database, including 6 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00075 ( 1 hom., cov: 33)

Exomes 𝑓: 0.00044 ( 5 hom. )

Consequence

MED16
NM_005481.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.50

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.021963388).

BS2

High Homozygotes in GnomAdExome4 at 5 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MED16	NM_005481.3 linkuse as main transcript	c.2365G>A	p.Ala789Thr	missense_variant	14/16	ENST00000325464.6	NP_005472.2	Q9Y2X0-1
MED16	XM_017026120.3 linkuse as main transcript	c.2158G>A	p.Ala720Thr	missense_variant	13/15		XP_016881609.1
MED16	XM_047438010.1 linkuse as main transcript	c.2158G>A	p.Ala720Thr	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.2365G>A	p.Ala789Thr	missense_variant	14/16	5	NM_005481.3	ENSP00000325612.1		Q9Y2X0-1

Frequencies

GnomAD3 genomes

AF:

0.000749

AC:

114

AN:

152216

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000145

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00164

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000385

Gnomad SAS

AF:

0.000828

Gnomad FIN

AF:

0.000188

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.00107

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.000689

AC:

111

AN:

161102

Hom.:

AF XY:

0.000777

AC XY:

AN XY:

86264

show subpopulations

Gnomad AFR exome

AF:

0.000294

Gnomad AMR exome

AF:

0.000832

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00110

Gnomad SAS exome

AF:

0.00143

Gnomad FIN exome

AF:

0.000371

Gnomad NFE exome

AF:

0.000490

Gnomad OTH exome

AF:

0.000895

GnomAD4 exome

AF:

0.000437

AC:

612

AN:

1399172

Hom.:

Cov.:

AF XY:

0.000464

AC XY:

321

AN XY:

691668

show subpopulations

Gnomad4 AFR exome

AF:

0.000278

Gnomad4 AMR exome

AF:

0.000626

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000322

Gnomad4 SAS exome

AF:

0.00126

Gnomad4 FIN exome

AF:

0.000190

Gnomad4 NFE exome

AF:

0.000387

Gnomad4 OTH exome

AF:

0.000515

GnomAD4 genome

AF:

0.000748

AC:

114

AN:

152334

Hom.:

Cov.:

AF XY:

0.000738

AC XY:

AN XY:

74494

show subpopulations

Gnomad4 AFR

AF:

0.000144

Gnomad4 AMR

AF:

0.00163

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000386

Gnomad4 SAS

AF:

0.000829

Gnomad4 FIN

AF:

0.000188

Gnomad4 NFE

AF:

0.00107

Gnomad4 OTH

AF:

0.000473

Alfa

AF:

0.00104

Hom.:

Bravo

AF:

0.000521

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000353

AC:

ExAC

AF:

0.000379

AC:

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

Dec 13, 2021

The c.2365G>A (p.A789T) alteration is located in exon 14 (coding exon 13) of the MED16 gene. This alteration results from a G to A substitution at nucleotide position 2365, causing the alanine (A) at amino acid position 789 to be replaced by a threonine (T). 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

0.084

BayesDel_addAF

Benign

-0.44

BayesDel_noAF

Benign

-0.40

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.048

.;.;T;T

Eigen

Benign

0.025

Eigen_PC

Benign

0.052

FATHMM_MKL

Uncertain

0.95

LIST_S2

Uncertain

0.86

D;D;.;D

M_CAP

Benign

0.023

MetaRNN

Benign

0.022

T;T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.46

N;.;N;N

MutationTaster

Benign

0.99

D;D;D;D;D

PrimateAI

Uncertain

0.59

PROVEAN

Benign

-0.90

N;N;.;N

REVEL

Benign

0.072

Sift

Benign

0.38

T;T;.;T

Sift4G

Benign

0.36

T;T;T;T

Polyphen

0.94, 0.95

.;P;P;P

Vest4

0.25

MVP

0.43

ClinPred

0.026

GERP RS

4.7

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.13

gMVP

0.42

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over