3-185424069-C-T

Position:

• chr3-185424069-C-T

Variant summary

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

The NM_004721.5(MAP3K13):​c.-85-4428C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.127 in 152,116 control chromosomes in the GnomAD database, including 1,563 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 0.13 (1563 hom., cov: 32)
• Consequence: MAP3K13 NM_004721.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0620

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=-0.83).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.241 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MAP3K13	NM_004721.5	c.-85-4428C>T		intron_variant		ENST00000265026.8	NP_004712.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MAP3K13	ENST00000265026.8	c.-85-4428C>T		intron_variant		1	NM_004721.5	ENSP00000265026.3

Frequencies

GnomAD3 genomes AF: 0.127 AC: 19314 AN: 151998 Hom.: 1564 Cov.: 32

Gnomad AFR AF: 0.0348

Gnomad AMI AF: 0.200

Gnomad AMR AF: 0.149

Gnomad ASJ AF: 0.155

Gnomad EAS AF: 0.222

Gnomad SAS AF: 0.252

Gnomad FIN AF: 0.184

Gnomad MID AF: 0.146

Gnomad NFE AF: 0.151

Gnomad OTH AF: 0.134

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

GnomAD4 genome AF: 0.127 AC: 19316 AN: 152116 Hom.: 1563 Cov.: 32 AF XY: 0.133 AC XY: 9899 AN XY: 74352

Gnomad4 AFR AF: 0.0347

Gnomad4 AMR AF: 0.149

Gnomad4 ASJ AF: 0.155

Gnomad4 EAS AF: 0.221

Gnomad4 SAS AF: 0.253

Gnomad4 FIN AF: 0.184

Gnomad4 NFE AF: 0.151

Gnomad4 OTH AF: 0.134

Alfa AF: 0.146 Hom.: 2376

Bravo AF: 0.116

Asia WGS AF: 0.206 AC: 719 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	4.9
DANN	Benign	0.70

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: rs7629245; hg19: chr3-185141857;