rs1129156

Variant names:

• chr19-40213169-T-C
• rs1129156
• NM_002446.4:c.1818T>C

Your query was ambiguous. Multiple possible variants found:

• chr19-40213169-T-C
• chr19-40213169-T-G

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_002446.4(MAP3K10):​c.1818T>C​(p.Phe606Phe) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.735 in 1,582,998 control chromosomes in the GnomAD database, including 428,731 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 0.75 (43064 hom., cov: 33)
  • Exomes 𝑓: 0.73 (385667 hom.)
• Consequence: MAP3K10 NM_002446.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.279
• Publications: 24 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 -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.61).
• BP7: Synonymous conserved (PhyloP=-0.279 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.8 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.1818T>C	p.Phe606Phe	synonymous	Exon 8 of 10	NP_002437.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MAP3K10	ENST00000253055.8	TSL:1 MANE Select	c.1818T>C	p.Phe606Phe	synonymous	Exon 8 of 10	ENSP00000253055.2	Q02779
	MAP3K10	ENST00000856942.1		c.1842T>C	p.Phe614Phe	synonymous	Exon 8 of 10	ENSP00000527002.1
	MAP3K10	ENST00000941194.1		c.1836T>C	p.Phe612Phe	synonymous	Exon 8 of 10	ENSP00000611253.1

Frequencies

GnomAD3 genomes AF: 0.751 AC: 114089 AN: 152016 Hom.: 43030 Cov.: 33

Gnomad AFR AF: 0.807

Gnomad AMI AF: 0.808

Gnomad AMR AF: 0.764

Gnomad ASJ AF: 0.643

Gnomad EAS AF: 0.693

Gnomad SAS AF: 0.777

Gnomad FIN AF: 0.696

Gnomad MID AF: 0.725

Gnomad NFE AF: 0.729

Gnomad OTH AF: 0.742

GnomAD2 exomes AF: 0.733 AC: 147839 AN: 201660 AF XY: 0.732

Gnomad AFR exome AF: 0.804

Gnomad AMR exome AF: 0.767

Gnomad ASJ exome AF: 0.633

Gnomad EAS exome AF: 0.698

Gnomad FIN exome AF: 0.696

Gnomad NFE exome AF: 0.725

Gnomad OTH exome AF: 0.727

GnomAD4 exome AF: 0.734 AC: 1049765 AN: 1430864 Hom.: 385667 Cov.: 48 AF XY: 0.734 AC XY: 519942 AN XY: 708630

African (AFR) AF: 0.806 AC: 26755 AN: 33186

American (AMR) AF: 0.764 AC: 29198 AN: 38198

Ashkenazi Jewish (ASJ) AF: 0.633 AC: 16031 AN: 25326

East Asian (EAS) AF: 0.683 AC: 26525 AN: 38818

South Asian (SAS) AF: 0.772 AC: 63020 AN: 81624

European-Finnish (FIN) AF: 0.700 AC: 35635 AN: 50930

Middle Eastern (MID) AF: 0.725 AC: 4137 AN: 5706

European-Non Finnish (NFE) AF: 0.733 AC: 804648 AN: 1097620

Other (OTH) AF: 0.737 AC: 43816 AN: 59456

GnomAD4 genome AF: 0.751 AC: 114188 AN: 152134 Hom.: 43064 Cov.: 33 AF XY: 0.748 AC XY: 55594 AN XY: 74344

African (AFR) AF: 0.807 AC: 33510 AN: 41536

American (AMR) AF: 0.764 AC: 11691 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.643 AC: 2232 AN: 3470

East Asian (EAS) AF: 0.693 AC: 3556 AN: 5134

South Asian (SAS) AF: 0.776 AC: 3742 AN: 4820

European-Finnish (FIN) AF: 0.696 AC: 7368 AN: 10592

Middle Eastern (MID) AF: 0.721 AC: 212 AN: 294

European-Non Finnish (NFE) AF: 0.729 AC: 49576 AN: 67970

Other (OTH) AF: 0.741 AC: 1564 AN: 2112

Alfa AF: 0.734 Hom.: 36762

Bravo AF: 0.757

Asia WGS AF: 0.743 AC: 2585 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.61
CADD	Benign	1.5
DANN	Benign	0.79
PhyloP100		-0.28
Mutation Taster		=100/0	polymorphism (auto)

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: rs1129156; hg19: chr19-40719076; COSMIC: COSV53423499; COSMIC: COSV53423499;