19-38595489-T-A

Position:

• chr19-38595489-T-A

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001042600.3(MAP4K1):​c.2336A>T​(p.Asp779Val) 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. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: MAP4K1 NM_001042600.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.67

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]

MAP4K1 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.2966146).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MAP4K1	NM_001042600.3	c.2336A>T	p.Asp779Val	missense_variant	29/31	ENST00000396857.7	NP_001036065.1
MAP4K1	NM_007181.6	c.2336A>T	p.Asp779Val	missense_variant	29/32		NP_009112.1
MAP4K1	XM_011526404.2	c.2456A>T	p.Asp819Val	missense_variant	30/32		XP_011524706.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MAP4K1	ENST00000396857.7	c.2336A>T	p.Asp779Val	missense_variant	29/31	5	NM_001042600.3	ENSP00000380066.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

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

Mar 29, 2023

The c.2336A>T (p.D779V) alteration is located in exon 29 (coding exon 29) of the MAP4K1 gene. This alteration results from a A to T substitution at nucleotide position 2336, causing the aspartic acid (D) at amino acid position 779 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	Benign	0.28
BayesDel_addAF	Uncertain	0.015	T
BayesDel_noAF	Benign	-0.22
CADD	Uncertain	25
DANN	Uncertain	0.99
DEOGEN2	Benign	0.23	T;T;T;.
Eigen	Uncertain	0.26
Eigen_PC	Uncertain	0.28
FATHMM_MKL	Benign	0.60	D
M_CAP	Benign	0.048	D
MetaRNN	Benign	0.30	T;T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.8	L;.;.;L
PrimateAI	Uncertain	0.59	T
PROVEAN	Uncertain	-3.4	.;.;.;D
REVEL	Benign	0.14
Sift	Uncertain	0.019	.;.;.;D
Sift4G	Benign	0.067	T;D;T;T
Polyphen		0.81	P;.;.;P
Vest4		0.48
MutPred		0.57		Loss of loop (P = 0.0203);.;.;Loss of loop (P = 0.0203);
MVP		0.80
MPC		2.5
ClinPred		0.97	D
GERP RS		5.1
Varity_R		0.24
gMVP		0.43

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: chr19-39086129;