2-134964910-C-T

Variant names:

• chr2-134964910-C-T
• rs150711518
• NM_025052.5:c.3927G>A

Variant summary

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

The NM_025052.5(MAP3K19):​c.3927G>A​(p.Gln1309Gln) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000685 in 1,459,554 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: 33)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: MAP3K19 NM_025052.5 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.587
• Publications: 0 publications found

Genes affected

MAP3K19 (HGNC:26249): (mitogen-activated protein kinase kinase kinase 19) Predicted to enable ATP binding activity; protein serine kinase activity; and protein serine/threonine kinase activity. Predicted to be involved in protein phosphorylation. [provided by Alliance of Genome Resources, Apr 2022]

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=-0.35).
• BP7: Synonymous conserved (PhyloP=0.587 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_025052.5. 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
	MAP3K19	NM_025052.5	MANE Select	c.3927G>A	p.Gln1309Gln	synonymous	Exon 13 of 13	NP_079328.3	Q56UN5-1
	MAP3K19	NM_001400438.1		c.3927G>A	p.Gln1309Gln	synonymous	Exon 13 of 13	NP_001387367.1	Q56UN5-1
	MAP3K19	NM_001018044.3		c.3588G>A	p.Gln1196Gln	synonymous	Exon 8 of 8	NP_001018054.1	Q56UN5-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MAP3K19	ENST00000392915.7	TSL:5 MANE Select	c.3927G>A	p.Gln1309Gln	synonymous	Exon 13 of 13	ENSP00000376647.2	Q56UN5-1
	MAP3K19	ENST00000375845.8	TSL:1	c.3927G>A	p.Gln1309Gln	synonymous	Exon 10 of 10	ENSP00000365005.3	Q56UN5-1
	MAP3K19	ENST00000358371.9	TSL:1	c.3588G>A	p.Gln1196Gln	synonymous	Exon 8 of 8	ENSP00000351140.4	Q56UN5-3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.85e-7 AC: 1 AN: 1459554 Hom.: 0 Cov.: 29 AF XY: 0.00000138 AC XY: 1 AN XY: 726016

African (AFR) AF: 0.00 AC: 0 AN: 33452

American (AMR) AF: 0.00 AC: 0 AN: 44534

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26068

East Asian (EAS) AF: 0.00 AC: 0 AN: 39656

South Asian (SAS) AF: 0.00 AC: 0 AN: 85794

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53346

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5762

European-Non Finnish (NFE) AF: 9.00e-7 AC: 1 AN: 1110704

Other (OTH) AF: 0.00 AC: 0 AN: 60238

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.35
CADD	Benign	8.6
DANN	Benign	0.65
PhyloP100		0.59
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs150711518; hg19: chr2-135722480;