3-185477339-CC-GT

Variant names:

• chr3-185477339-CC-GT
• NM_004721.5:c.2444_2445delCCinsGT
• MAP3K13 p.Ser815Cys

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 1P and 0B. PP3

The NM_004721.5(MAP3K13):​c.2444_2445delCCinsGT​(p.Ser815Cys) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. It is difficult to determine the true allele frequency of this variant because it is of type MNV, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: MAP3K13 NM_004721.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.75
• Publications: 0 publications found

Genes affected

MAP3K13 (HGNC:6852): (mitogen-activated protein kinase kinase kinase 13) The protein encoded by this gene is a member of serine/threonine protein kinase family. This kinase contains a dual leucine-zipper motif, and has been shown to form dimers/oligomers through its leucine-zipper motif. This kinase can phosphorylate and activate MAPK8/JNK, MAP2K7/MKK7, which suggests a role in the JNK signaling pathway. [provided by RefSeq, Jul 2008]

LOC101929018 (HGNC:):

TMEM41A (HGNC:30544): (transmembrane protein 41A) Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PP3: No computational evidence supports a deleterious effect, but strongly conserved according to phyloP

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004721.5. 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
	MAP3K13	NM_004721.5	MANE Select	c.2444_2445delCCinsGT	p.Ser815Cys	missense	N/A	NP_004712.1	O43283-1
	MAP3K13	NM_001242314.2		c.2444_2445delCCinsGT	p.Ser815Cys	missense	N/A	NP_001229243.1	O43283-1
	MAP3K13	NM_001242317.2		c.1823_1824delCCinsGT	p.Ser608Cys	missense	N/A	NP_001229246.1	O43283-5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MAP3K13	ENST00000265026.8	TSL:1 MANE Select	c.2444_2445delCCinsGT	p.Ser815Cys	missense	N/A	ENSP00000265026.3	O43283-1
	MAP3K13	ENST00000424227.5	TSL:1	c.2444_2445delCCinsGT	p.Ser815Cys	missense	N/A	ENSP00000399910.1	O43283-1
	MAP3K13	ENST00000438053.5	TSL:1	n.*1585_*1586delCCinsGT		non_coding_transcript_exon	Exon 10 of 12	ENSP00000403561.1	O43283-3

Frequencies

GnomAD3 genomes Cov.: 32

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		7.8

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr3-185195127;