Variant 19-868421-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_005481.3(MED16):c.2478C>T(p.Asn826=) variant causes a synonymous change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00389 in 1,610,342 control chromosomes in the GnomAD database, including 190 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.020 ( 93 hom., cov: 33)

Exomes 𝑓: 0.0022 ( 97 hom. )

Consequence

MED16
NM_005481.3 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 7.45

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 -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.55).

BP6

Variant 19-868421-G-A is Benign according to our data. Variant chr19-868421-G-A is described in ClinVar as [Benign]. Clinvar id is 780494.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0673 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
MED16	NM_005481.3 linkuse as main transcript	c.2478C>T	p.Asn826=	synonymous_variant	15/16	ENST00000325464.6	NP_005472.2
MED16	XM_017026120.3 linkuse as main transcript	c.2271C>T	p.Asn757=	synonymous_variant	14/15		XP_016881609.1
MED16	XM_047438010.1 linkuse as main transcript	c.2271C>T	p.Asn757=	synonymous_variant	14/14		XP_047293966.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MED16	ENST00000325464.6 linkuse as main transcript	c.2478C>T	p.Asn826=	synonymous_variant	15/16	5	NM_005481.3	ENSP00000325612		Q9Y2X0-1

Frequencies

GnomAD3 genomes

AF:

0.0202

AC:

3077

AN:

152186

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0694

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0105

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.000118

Gnomad OTH

AF:

0.0139

GnomAD3 exomes

AF:

0.00556

AC:

1376

AN:

247428

Hom.:

AF XY:

0.00437

AC XY:

588

AN XY:

134624

show subpopulations

Gnomad AFR exome

AF:

0.0745

Gnomad AMR exome

AF:

0.00418

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000131

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000206

Gnomad OTH exome

AF:

0.00181

GnomAD4 exome

AF:

0.00218

AC:

3172

AN:

1458038

Hom.:

Cov.:

AF XY:

0.00195

AC XY:

1411

AN XY:

725444

show subpopulations

Gnomad4 AFR exome

AF:

0.0752

Gnomad4 AMR exome

AF:

0.00501

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000104

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000111

Gnomad4 OTH exome

AF:

0.00437

GnomAD4 genome

AF:

0.0203

AC:

3086

AN:

152304

Hom.:

Cov.:

AF XY:

0.0195

AC XY:

1454

AN XY:

74476

show subpopulations

Gnomad4 AFR

AF:

0.0694

Gnomad4 AMR

AF:

0.0105

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000118

Gnomad4 OTH

AF:

0.0137

Alfa

AF:

0.00703

Hom.:

Bravo

AF:

0.0237

Asia WGS

AF:

0.00577

AC:

AN:

3478

EpiCase

AF:

0.000273

EpiControl

AF:

0.000534

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Aug 01, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.55

CADD

Benign

7.1

DANN

Benign

0.91

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