2-134980864-A-C

Position:

• chr2-134980864-A-C

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_025052.5(MAP3K19):​c.3877T>G​(p.Phe1293Val) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: 9.09

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

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MAP3K19	NM_025052.5	c.3877T>G	p.Phe1293Val	missense_variant	12/13	ENST00000392915.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MAP3K19	ENST00000392915.7	c.3877T>G	p.Phe1293Val	missense_variant	12/13	5	NM_025052.5	P2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

May 28, 2024

The c.3877T>G (p.F1293V) alteration is located in exon 9 (coding exon 9) of the MAP3K19 gene. This alteration results from a T to G substitution at nucleotide position 3877, causing the phenylalanine (F) at amino acid position 1293 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.61
BayesDel_addAF	Pathogenic	0.17	D
BayesDel_noAF	Uncertain	0.0
CADD	Pathogenic	26
DANN	Uncertain	0.99
DEOGEN2	Benign	0.021	T;T;.;.;.;.;.
Eigen	Uncertain	0.48
Eigen_PC	Uncertain	0.57
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Benign	0.82	.;T;D;T;T;D;T
M_CAP	Benign	0.037	D
MetaRNN	Uncertain	0.59	D;D;D;D;D;D;D
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.42	N;N;.;.;.;.;.
MutationTaster	Benign	1.0	D;D;D;D;D;D;D
PrimateAI	Uncertain	0.60	T
PROVEAN	Pathogenic	-5.3	.;D;D;D;D;D;D
REVEL	Uncertain	0.46
Sift	Benign	0.035	.;D;T;D;T;T;T
Sift4G	Uncertain	0.024	.;D;T;D;T;T;D
Polyphen		1.0	D;D;.;D;D;P;.
Vest4		0.70, 0.83, 0.82, 0.82
MutPred		0.47		Gain of disorder (P = 0.2277);Gain of disorder (P = 0.2277);.;.;.;.;.;
MVP		0.56
MPC		0.62
ClinPred		0.99	D
GERP RS		5.6
Varity_R		0.51
gMVP		0.77

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr2-135738434;