19-38614071-G-GA

Position:

• chr19-38614071-G-GA

Variant summary

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

The NM_001042600.3(MAP4K1):​c.431_432insT​(p.Ile145HisfsTer3) variant causes a frameshift change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Variant results in nonsense mediated mRNA decay.

• Frequency: Genomes: not found (cov: 31)
• Consequence: MAP4K1 NM_001042600.3 frameshift
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 8.33

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]

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	Protein	UniProt
MAP4K1	NM_001042600.3	c.431_432insT	p.Ile145HisfsTer3	frameshift_variant	7/31	ENST00000396857.7	NP_001036065.1
MAP4K1	NM_007181.6	c.431_432insT	p.Ile145HisfsTer3	frameshift_variant	7/32		NP_009112.1
MAP4K1	XM_011526404.2	c.431_432insT	p.Ile145HisfsTer3	frameshift_variant	7/32		XP_011524706.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MAP4K1	ENST00000396857.7	c.431_432insT	p.Ile145HisfsTer3	frameshift_variant	7/31	5	NM_001042600.3	ENSP00000380066	P1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 34

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

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

LitVar

Other links and lift over

dbSNP: rs35958189; hg19: chr19-39104711;