rs892117

Variant names:

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

Your query was ambiguous. Multiple possible variants found:

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

Variant summary

Our verdict is Benign. The variant received -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
• 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: Benign. The variant received -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.

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>G		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>G		intron	N/A	ENSP00000253055.2	Q02779
	MAP3K10	ENST00000856942.1		c.1212+130A>G		intron	N/A	ENSP00000527002.1
	MAP3K10	ENST00000941194.1		c.1206+112A>G		intron	N/A	ENSP00000611253.1

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

African (AFR) AF: 0.0934 AC: 1734 AN: 18556

American (AMR) AF: 0.565 AC: 10952 AN: 19396

Ashkenazi Jewish (ASJ) AF: 0.387 AC: 6025 AN: 15586

East Asian (EAS) AF: 0.475 AC: 15492 AN: 32600

South Asian (SAS) AF: 0.604 AC: 30741 AN: 50868

European-Finnish (FIN) AF: 0.429 AC: 18057 AN: 42138

Middle Eastern (MID) AF: 0.412 AC: 1424 AN: 3458

European-Non Finnish (NFE) AF: 0.510 AC: 284469 AN: 557504

Other (OTH) AF: 0.480 AC: 17409 AN: 36300

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

African (AFR) AF: 0.111 AC: 4597 AN: 41474

American (AMR) AF: 0.518 AC: 7912 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.395 AC: 1370 AN: 3472

East Asian (EAS) AF: 0.491 AC: 2532 AN: 5156

South Asian (SAS) AF: 0.612 AC: 2942 AN: 4808

European-Finnish (FIN) AF: 0.423 AC: 4464 AN: 10558

Middle Eastern (MID) AF: 0.432 AC: 127 AN: 294

European-Non Finnish (NFE) AF: 0.504 AC: 34260 AN: 67956

Other (OTH) AF: 0.407 AC: 859 AN: 2112

Alfa AF: 0.475 Hom.: 30155

Bravo AF: 0.384

Asia WGS AF: 0.523 AC: 1819 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.50
CADD	Benign	17
DANN	Benign	0.93
PhyloP100		-0.51
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs892117; hg19: chr19-40711333;