rs1347048724

Variant names:

• chr2-134981100-G-A
• rs1347048724
• NM_025052.5:c.3641C>T

Your query was ambiguous. Multiple possible variants found:

• chr2-134981100-G-A
• chr2-134981100-G-C

Variant summary

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

The NM_025052.5(MAP3K19):​c.3641C>T​(p.Ala1214Val) 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. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: MAP3K19 NM_025052.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.61
• 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: 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 (MetaRNN=0.1675323).

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.3641C>T	p.Ala1214Val	missense	Exon 12 of 13	NP_079328.3	Q56UN5-1
	MAP3K19	NM_001400438.1		c.3641C>T	p.Ala1214Val	missense	Exon 12 of 13	NP_001387367.1	Q56UN5-1
	MAP3K19	NM_001018044.3		c.3302C>T	p.Ala1101Val	missense	Exon 7 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.3641C>T	p.Ala1214Val	missense	Exon 12 of 13	ENSP00000376647.2	Q56UN5-1
	MAP3K19	ENST00000375845.8	TSL:1	c.3641C>T	p.Ala1214Val	missense	Exon 9 of 10	ENSP00000365005.3	Q56UN5-1
	MAP3K19	ENST00000358371.9	TSL:1	c.3302C>T	p.Ala1101Val	missense	Exon 7 of 8	ENSP00000351140.4	Q56UN5-3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000756

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.15
BayesDel_addAF	Benign	-0.15	T
BayesDel_noAF	Benign	-0.46
CADD	Benign	21
DANN	Uncertain	0.99
DEOGEN2	Benign	0.0033	T
Eigen	Benign	0.014
Eigen_PC	Benign	0.18
FATHMM_MKL	Benign	0.67	D
LIST_S2	Uncertain	0.86	D
M_CAP	Benign	0.0039	T
MetaRNN	Benign	0.17	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.1	L
PhyloP100		2.6
PrimateAI	Benign	0.42	T
PROVEAN	Benign	-1.2	N
REVEL	Benign	0.038
Sift	Benign	0.094	T
Sift4G	Uncertain	0.059	T
Polyphen		0.72	P
Vest4		0.24
MutPred		0.35		Loss of sheet (P = 0.1158)
MVP		0.62
MPC		0.14
ClinPred		0.67	D
GERP RS		3.9
Varity_R		0.068
gMVP		0.26
Mutation Taster		=87/13	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: rs1347048724; hg19: chr2-135738670;