19-40205426-A-T

Variant names:

• chr19-40205426-A-T
• rs892117
• NM_002446.4:c.1188+130A>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_002446.4(MAP3K10):​c.1188+130A>T variant causes a intron 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000013 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: MAP3K10 NM_002446.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.511
• Publications: 9 publications found

Genes affected

MAP3K10 (HGNC:6849): (mitogen-activated protein kinase kinase kinase 10) The protein encoded by this gene is a member of the serine/threonine kinase family. This kinase has been shown to activate MAPK8/JNK and MKK4/SEK1, and this kinase itself can be phoshorylated, and thus activated by JNK kinases. This kinase functions preferentially on the JNK signaling pathway, and is reported to be involved in nerve growth factor (NGF) induced neuronal apoptosis. [provided by RefSeq, Jul 2008]

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.52).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002446.4. 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
	MAP3K10	NM_002446.4	MANE Select	c.1188+130A>T		intron	N/A	NP_002437.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MAP3K10	ENST00000253055.8	TSL:1 MANE Select	c.1188+130A>T		intron	N/A	ENSP00000253055.2	Q02779
	MAP3K10	ENST00000856942.1		c.1212+130A>T		intron	N/A	ENSP00000527002.1
	MAP3K10	ENST00000941194.1		c.1206+112A>T		intron	N/A	ENSP00000611253.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00000128 AC: 1 AN: 778300 Hom.: 0 Cov.: 10 AF XY: 0.00 AC XY: 0 AN XY: 391680

African (AFR) AF: 0.00 AC: 0 AN: 18566

American (AMR) AF: 0.0000515 AC: 1 AN: 19414

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 15606

East Asian (EAS) AF: 0.00 AC: 0 AN: 32626

South Asian (SAS) AF: 0.00 AC: 0 AN: 50962

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 42194

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3468

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 559078

Other (OTH) AF: 0.00 AC: 0 AN: 36386

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 30155

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.52
CADD	Benign	14
DANN	Benign	0.89
PhyloP100		-0.51

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs892117; hg19: chr19-40711333;