19-871054-C-T

Variant names:

• chr19-871054-C-T
• rs1188100993
• ENST00000607471.5:c.1364G>A

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The ENST00000607471.5(MED16):​c.1364G>A​(p.Ser455Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 6/7 in silico tools predict a benign outcome for this variant. 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. S455I) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 33)
• Consequence: MED16 ENST00000607471.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0960
• Publications: 0 publications found

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 Gene-Disease associations (from GenCC):

• complex neurodevelopmental disorder with or without congenital anomalies

  Inheritance: AR Classification: MODERATE Submitted by: Ambry Genetics

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (REVEL=0.036).

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000607471.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MED16	NM_005481.3	MANE Select	c.2298G>A	p.Gln766Gln	synonymous	Exon 13 of 16	NP_005472.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MED16	ENST00000607471.5	TSL:1	c.1364G>A	p.Ser455Asn	missense	Exon 8 of 10	ENSP00000475725.1	U3KQB4
	MED16	ENST00000325464.6	TSL:5 MANE Select	c.2298G>A	p.Gln766Gln	synonymous	Exon 13 of 16	ENSP00000325612.1	Q9Y2X0-1
	MED16	ENST00000312090.10	TSL:1	c.2355G>A	p.Gln785Gln	synonymous	Exon 14 of 16	ENSP00000308528.4	Q9Y2X0-3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.65
CADD	Benign	0.75
DANN	Benign	0.97
PhyloP100		0.096
PromoterAI		0.012	Neutral

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

Other links and lift over

dbSNP: rs1188100993; hg19: chr19-871054;