19-38587810-C-T

Position:

• chr19-38587810-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP6_Moderate

The NM_001042600.3(MAP4K1):​c.2404G>A​(p.Val802Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Likely benign (★).

• Frequency: Genomes: not found (cov: 31)
• Consequence: MAP4K1 NM_001042600.3 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 2.87

Genes affected

MAP4K1 (HGNC:6863): (mitogen-activated protein kinase kinase kinase kinase 1) Enables ATP binding activity and MAP kinase kinase kinase kinase activity. Involved in several processes, including JNK cascade; cellular response to phorbol 13-acetate 12-myristate; and protein phosphorylation. Located in membrane. [provided by Alliance of Genome Resources, Apr 2022]

RYR1 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP6: Variant 19-38587810-C-T is Benign according to our data. Variant chr19-38587810-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 3123073.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MAP4K1	NM_001042600.3	c.2404G>A	p.Val802Met	missense_variant	31/31	ENST00000396857.7	NP_001036065.1
MAP4K1	XM_011526404.2	c.2524G>A	p.Val842Met	missense_variant	32/32		XP_011524706.1
MAP4K1	NM_007181.6	c.2502G>A	p.Ter834Ter	stop_retained_variant	32/32		NP_009112.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MAP4K1	ENST00000396857.7	c.2404G>A	p.Val802Met	missense_variant	31/31	5	NM_001042600.3	ENSP00000380066.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 31

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 19, 2023

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Uncertain	0.15	D
BayesDel_noAF	Uncertain	-0.020
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.0091	T;T;.
Eigen	Pathogenic	0.88
Eigen_PC	Pathogenic	0.71
FATHMM_MKL	Uncertain	0.88	D
M_CAP	Pathogenic	0.56	D
MetaRNN	Uncertain	0.62	D;D;D
MetaSVM	Uncertain	0.19	D
PROVEAN	Benign	-1.9	.;.;N
REVEL	Uncertain	0.49
Sift	Benign	0.089	.;.;T
Sift4G	Uncertain	0.014	D;T;T
Polyphen		0.99	.;.;D
Vest4		0.36
MutPred		0.43		.;.;Gain of catalytic residue at V802 (P = 0.0696);
MVP		0.95
ClinPred		0.51	D
GERP RS		4.1

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: chr19-39078450;