2-134986265-C-A

Position:

• chr2-134986265-C-A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_025052.5(MAP3K19):​c.2607G>T​(p.Gln869His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000205 in 1,461,672 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 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)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: MAP3K19 NM_025052.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -3.11

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]

MAP3K19 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.09178287).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MAP3K19	NM_025052.5	c.2607G>T	p.Gln869His	missense_variant	10/13	ENST00000392915.7	NP_079328.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MAP3K19	ENST00000392915.7	c.2607G>T	p.Gln869His	missense_variant	10/13	5	NM_025052.5	ENSP00000376647.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000205 AC: 3 AN: 1461672 Hom.: 0 Cov.: 33 AF XY: 0.00000138 AC XY: 1 AN XY: 727122

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000270

Gnomad4 OTH exome AF: 0.00

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

Jan 03, 2024

The c.2607G>T (p.Q869H) alteration is located in exon 7 (coding exon 7) of the MAP3K19 gene. This alteration results from a G to T substitution at nucleotide position 2607, causing the glutamine (Q) at amino acid position 869 to be replaced by a histidine (H). 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	Benign	0.11
BayesDel_addAF	Benign	-0.25	T
BayesDel_noAF	Benign	-0.60
CADD	Benign	0.040
DANN	Benign	0.93
DEOGEN2	Benign	0.0020	T;T;.;.;.
Eigen	Benign	-0.83
Eigen_PC	Benign	-1.0
FATHMM_MKL	Benign	0.017	N
LIST_S2	Benign	0.71	.;T;T;T;T
M_CAP	Benign	0.069	D
MetaRNN	Benign	0.092	T;T;T;T;T
MetaSVM	Benign	-0.79	T
MutationAssessor	Benign	1.0	L;L;.;.;.
PrimateAI	Benign	0.21	T
PROVEAN	Benign	-1.0	.;N;N;N;.
REVEL	Benign	0.16
Sift	Benign	0.052	.;T;T;T;.
Sift4G	Uncertain	0.022	.;D;D;T;.
Polyphen		0.91	P;P;P;.;.
Vest4		0.096, 0.065
MutPred		0.076		Loss of methylation at K866 (P = 0.1581);Loss of methylation at K866 (P = 0.1581);.;.;.;
MVP		0.75
MPC		0.25
ClinPred		0.41	T
GERP RS		-3.8
Varity_R		0.060
gMVP		0.042

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.070		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: chr2-135743835;