NM_001042600.3:c.431dupT

Variant names:

• chr19-38614071-G-GA
• rs35958189
• NM_001042600.3:c.431dupT

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_001042600.3(MAP4K1):​c.431dupT​(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
• Publications: 2 publications found

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

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001042600.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MAP4K1	NM_001042600.3	MANE Select	c.431dupT	p.Ile145HisfsTer3	frameshift	Exon 7 of 31	NP_001036065.1	Q92918-2
	MAP4K1	NM_007181.6		c.431dupT	p.Ile145HisfsTer3	frameshift	Exon 7 of 32	NP_009112.1	Q92918-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MAP4K1	ENST00000396857.7	TSL:5 MANE Select	c.431dupT	p.Ile145HisfsTer3	frameshift	Exon 7 of 31	ENSP00000380066.1	Q92918-2
	MAP4K1	ENST00000591517.5	TSL:1	c.431dupT	p.Ile145HisfsTer3	frameshift	Exon 7 of 32	ENSP00000465039.1	Q92918-1
	MAP4K1	ENST00000864511.1		c.431dupT	p.Ile145HisfsTer3	frameshift	Exon 7 of 32	ENSP00000534570.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 34

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		8.3

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

Other links and lift over

dbSNP: rs35958189; hg19: chr19-39104711;