11-57704768-C-T

Variant names:

• chr11-57704768-C-T
• rs781537069
• NM_001317078.4:c.522G>A

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 2P and 3B. PM2 BP4_Moderate BP7

The NM_001317078.4(MED19):​c.522G>A​(p.Lys174Lys) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000718 in 1,393,684 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 30)
  • Exomes 𝑓: 7.2e-7 (0 hom.)
• Consequence: MED19 NM_001317078.4 synonymous
• 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: Likely_benign. The variant received -1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.43).
• BP7: Synonymous conserved (PhyloP=1.47 with no splicing effect.

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>A	p.Lys174Lys	synonymous	Exon 3 of 5	NP_001304007.2	J3KR33
	MED19	NM_153450.4		c.522G>A	p.Lys174Lys	synonymous	Exon 3 of 4	NP_703151.3	A0JLT2-2
	MED19	NR_157587.1		n.558G>A		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>A	p.Lys174Lys	synonymous	Exon 3 of 5	ENSP00000416227.4	J3KR33
	MED19	ENST00000337672.9	TSL:1	c.522G>A	p.Lys174Lys	synonymous	Exon 3 of 4	ENSP00000337340.4	A0JLT2-2
	MED19	ENST00000534677.1	TSL:1	n.721G>A		non_coding_transcript_exon	Exon 2 of 2

Frequencies

GnomAD3 genomes Cov.: 30

GnomAD4 exome AF: 7.18e-7 AC: 1 AN: 1393684 Hom.: 0 Cov.: 35 AF XY: 0.00000144 AC XY: 1 AN XY: 692302

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 31694

American (AMR) AF: 0.00 AC: 0 AN: 42562

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 23638

East Asian (EAS) AF: 0.00 AC: 0 AN: 34958

South Asian (SAS) AF: 0.00 AC: 0 AN: 85604

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 47798

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5388

European-Non Finnish (NFE) AF: 9.38e-7 AC: 1 AN: 1066086

Other (OTH) AF: 0.00 AC: 0 AN: 55956

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 30

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.43
CADD	Benign	9.7
DANN	Benign	0.84
PhyloP100		1.5

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: rs781537069; hg19: chr11-57472240;