rs13099317

Variant names:

• chr3-185417660-G-A
• rs13099317
• NM_004721.5:c.-85-10837G>A

Variant summary

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

The NM_004721.5(MAP3K13):​c.-85-10837G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.648 in 1,611,464 control chromosomes in the GnomAD database, including 343,436 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 0.58 (26662 hom., cov: 31)
  • Exomes 𝑓: 0.65 (316774 hom.)
• Consequence: MAP3K13 NM_004721.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.513

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]

RPL4P4 (HGNC:36179): (ribosomal protein L4 pseudogene 4)

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.67).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.678 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MAP3K13	NM_004721.5	c.-85-10837G>A		intron_variant	Intron 1 of 13	ENST00000265026.8	NP_004712.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MAP3K13	ENST00000265026.8	c.-85-10837G>A		intron_variant	Intron 1 of 13	1	NM_004721.5	ENSP00000265026.3

Frequencies

GnomAD3 genomes AF: 0.580 AC: 88036 AN: 151742 Hom.: 26646 Cov.: 31

Gnomad AFR AF: 0.409

Gnomad AMI AF: 0.738

Gnomad AMR AF: 0.582

Gnomad ASJ AF: 0.707

Gnomad EAS AF: 0.458

Gnomad SAS AF: 0.513

Gnomad FIN AF: 0.613

Gnomad MID AF: 0.646

Gnomad NFE AF: 0.683

Gnomad OTH AF: 0.619

GnomAD4 exome AF: 0.655 AC: 955695 AN: 1459606 Hom.: 316774 Cov.: 54 AF XY: 0.652 AC XY: 473463 AN XY: 726116

Gnomad4 AFR exome AF: 0.398

Gnomad4 AMR exome AF: 0.561

Gnomad4 ASJ exome AF: 0.714

Gnomad4 EAS exome AF: 0.482

Gnomad4 SAS exome AF: 0.536

Gnomad4 FIN exome AF: 0.610

Gnomad4 NFE exome AF: 0.684

Gnomad4 OTH exome AF: 0.635

GnomAD4 genome AF: 0.580 AC: 88079 AN: 151858 Hom.: 26662 Cov.: 31 AF XY: 0.573 AC XY: 42555 AN XY: 74220

Gnomad4 AFR AF: 0.408

Gnomad4 AMR AF: 0.582

Gnomad4 ASJ AF: 0.707

Gnomad4 EAS AF: 0.459

Gnomad4 SAS AF: 0.514

Gnomad4 FIN AF: 0.613

Gnomad4 NFE AF: 0.683

Gnomad4 OTH AF: 0.621

Alfa AF: 0.644 Hom.: 5980

Bravo AF: 0.573

Asia WGS AF: 0.488 AC: 1695 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.67
CADD	Benign	8.8
DANN	Benign	0.90

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs13099317; hg19: chr3-185135448; COSMIC: COSV53984971;