rs892117

Positions:

• chr19-40205426-A-G
• chr19-40205426-A-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_002446.4(MAP3K10):​c.1188+130A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.48 in 928,414 control chromosomes in the GnomAD database, including 113,207 homozygotes. 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: 𝑓 0.39 (14096 hom., cov: 32)
  • Exomes 𝑓: 0.50 (99111 hom.)
• Consequence: MAP3K10 NM_002446.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.511

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.5).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.593 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MAP3K10	NM_002446.4	c.1188+130A>G		intron_variant		ENST00000253055.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MAP3K10	ENST00000253055.8	c.1188+130A>G		intron_variant		1	NM_002446.4	P1

Frequencies

GnomAD3 genomes AF: 0.392 AC: 59477 AN: 151888 Hom.: 14095 Cov.: 32

Gnomad AFR AF: 0.111

Gnomad AMI AF: 0.457

Gnomad AMR AF: 0.518

Gnomad ASJ AF: 0.395

Gnomad EAS AF: 0.491

Gnomad SAS AF: 0.612

Gnomad FIN AF: 0.423

Gnomad MID AF: 0.443

Gnomad NFE AF: 0.504

Gnomad OTH AF: 0.406

GnomAD4 exome AF: 0.498 AC: 386303 AN: 776406 Hom.: 99111 Cov.: 10 AF XY: 0.502 AC XY: 196106 AN XY: 390766

Gnomad4 AFR exome AF: 0.0934

Gnomad4 AMR exome AF: 0.565

Gnomad4 ASJ exome AF: 0.387

Gnomad4 EAS exome AF: 0.475

Gnomad4 SAS exome AF: 0.604

Gnomad4 FIN exome AF: 0.429

Gnomad4 NFE exome AF: 0.510

Gnomad4 OTH exome AF: 0.480

GnomAD4 genome AF: 0.391 AC: 59480 AN: 152008 Hom.: 14096 Cov.: 32 AF XY: 0.392 AC XY: 29137 AN XY: 74294

Gnomad4 AFR AF: 0.111

Gnomad4 AMR AF: 0.518

Gnomad4 ASJ AF: 0.395

Gnomad4 EAS AF: 0.491

Gnomad4 SAS AF: 0.612

Gnomad4 FIN AF: 0.423

Gnomad4 NFE AF: 0.504

Gnomad4 OTH AF: 0.407

Alfa AF: 0.487 Hom.: 24607

Bravo AF: 0.384

Asia WGS AF: 0.523 AC: 1819 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.50
CADD	Benign	17
DANN	Benign	0.93

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.15		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: rs892117; hg19: chr19-40711333;