11-57704768-C-G

Variant names:

• chr11-57704768-C-G
• NM_001317078.4:c.522G>C
• MED19 p.Lys174Asn

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001317078.4(MED19):​c.522G>C​(p.Lys174Asn) 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar.

• Frequency: Genomes: not found (cov: 30)
• Consequence: MED19 NM_001317078.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.47
• Publications: 0 publications found

Genes affected

MED19 (HGNC:29600): (mediator complex subunit 19) The protein encoded by this gene is a subunit of the Mediator complex, which binds to gene-specific regulatory factors and provides support for the basal RNA polymerase II transcription machinery. This gene has been implicated in the growth of several types of cancer, and inhibition of its expression inhibits the growth and spread of these cancers. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Nov 2015]

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.34261838).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001317078.4. 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
	MED19	NM_001317078.4	MANE Select	c.522G>C	p.Lys174Asn	missense	Exon 3 of 5	NP_001304007.2	J3KR33
	MED19	NM_153450.4		c.522G>C	p.Lys174Asn	missense	Exon 3 of 4	NP_703151.3	A0JLT2-2
	MED19	NR_157587.1		n.558G>C		non_coding_transcript_exon	Exon 3 of 5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MED19	ENST00000431606.5	TSL:1 MANE Select	c.522G>C	p.Lys174Asn	missense	Exon 3 of 5	ENSP00000416227.4	J3KR33
	MED19	ENST00000337672.9	TSL:1	c.522G>C	p.Lys174Asn	missense	Exon 3 of 4	ENSP00000337340.4	A0JLT2-2
	MED19	ENST00000534677.1	TSL:1	n.721G>C		non_coding_transcript_exon	Exon 2 of 2

Frequencies

GnomAD3 genomes Cov.: 30

GnomAD4 exome Cov.: 35

GnomAD4 genome Cov.: 30

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.87
BayesDel_addAF	Benign	-0.16	T
BayesDel_noAF	Benign	-0.47
CADD	Uncertain	24
DANN	Uncertain	1.0
Eigen	Uncertain	0.45
Eigen_PC	Uncertain	0.36
FATHMM_MKL	Uncertain	0.88	D
LIST_S2	Benign	0.81	T
M_CAP	Benign	0.0052	T
MetaRNN	Benign	0.34	T
MetaSVM	Benign	-0.55	T
PhyloP100		1.5
PrimateAI	Uncertain	0.69	T
REVEL	Benign	0.25
Mutation Taster		=33/67	disease causing

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr11-57472240;