19-868910-C-G

Variant names:

• chr19-868910-C-G
• NM_005481.3:c.2352G>C

Variant summary

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

The NM_005481.3(MED16):​c.2352G>C​(p.Arg784Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: MED16 NM_005481.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.33

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]

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
MED16	NM_005481.3	c.2352G>C	p.Arg784Ser	missense_variant	Exon 14 of 16	ENST00000325464.6	NP_005472.2
MED16	XM_017026120.3	c.2145G>C	p.Arg715Ser	missense_variant	Exon 13 of 15		XP_016881609.1
MED16	XM_047438010.1	c.2145G>C	p.Arg715Ser	missense_variant	Exon 13 of 14		XP_047293966.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MED16	ENST00000325464.6	c.2352G>C	p.Arg784Ser	missense_variant	Exon 14 of 16	5	NM_005481.3	ENSP00000325612.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Oct 26, 2021

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.2352G>C (p.R784S) alteration is located in exon 14 (coding exon 13) of the MED16 gene. This alteration results from a G to C substitution at nucleotide position 2352, causing the arginine (R) at amino acid position 784 to be replaced by a serine (S). 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	Pathogenic	0.94
BayesDel_addAF	Benign	0.0086	T
BayesDel_noAF	Benign	-0.23
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.094	.;.;T;T
Eigen	Benign	0.068
Eigen_PC	Benign	0.078
FATHMM_MKL	Uncertain	0.92	D
LIST_S2	Uncertain	0.90	D;D;.;D
M_CAP	Benign	0.023	T
MetaRNN	Uncertain	0.59	D;D;D;D
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.6	L;.;L;L
PrimateAI	Pathogenic	0.79	T
PROVEAN	Benign	-1.3	N;N;.;N
REVEL	Benign	0.12
Sift	Benign	0.060	T;T;.;T
Sift4G	Benign	0.33	T;T;T;T
Polyphen		0.73, 0.77	.;P;P;P
Vest4		0.74
MutPred		0.38		Gain of phosphorylation at R784 (P = 0.1032);.;Gain of phosphorylation at R784 (P = 0.1032);Gain of phosphorylation at R784 (P = 0.1032);
MVP		0.37
ClinPred		0.81	D
GERP RS		2.2
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.28
gMVP		0.46

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: chr19-868910;