3-185394871-A-G

Position:

• chr3-185394871-A-G

Variant summary

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

The NM_004721.5(MAP3K13):​c.-86+31503A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.703 in 151,898 control chromosomes in the GnomAD database, including 38,082 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 0.70 (38082 hom., cov: 30)
• Consequence: MAP3K13 NM_004721.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.891

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.78).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.767 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MAP3K13	NM_004721.5	c.-86+31503A>G		intron_variant		ENST00000265026.8	NP_004712.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MAP3K13	ENST00000265026.8	c.-86+31503A>G		intron_variant		1	NM_004721.5	ENSP00000265026	P1

Frequencies

GnomAD3 genomes AF: 0.703 AC: 106653 AN: 151780 Hom.: 38059 Cov.: 30

Gnomad AFR AF: 0.560

Gnomad AMI AF: 0.874

Gnomad AMR AF: 0.708

Gnomad ASJ AF: 0.809

Gnomad EAS AF: 0.672

Gnomad SAS AF: 0.748

Gnomad FIN AF: 0.740

Gnomad MID AF: 0.736

Gnomad NFE AF: 0.773

Gnomad OTH AF: 0.726

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

GnomAD4 genome AF: 0.703 AC: 106715 AN: 151898 Hom.: 38082 Cov.: 30 AF XY: 0.702 AC XY: 52124 AN XY: 74240

Gnomad4 AFR AF: 0.560

Gnomad4 AMR AF: 0.708

Gnomad4 ASJ AF: 0.809

Gnomad4 EAS AF: 0.673

Gnomad4 SAS AF: 0.749

Gnomad4 FIN AF: 0.740

Gnomad4 NFE AF: 0.773

Gnomad4 OTH AF: 0.728

Alfa AF: 0.751 Hom.: 28483

Bravo AF: 0.692

Asia WGS AF: 0.687 AC: 2385 AN: 3470

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	5.6
DANN	Benign	0.89

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

Publications

LitVar

Other links and lift over

dbSNP: rs4687299; hg19: chr3-185112659;