rs13099317

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 3 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004721.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MAP3K13	NM_004721.5	MANE Select	c.-85-10837G>A		intron	N/A	NP_004712.1
	MAP3K13	NM_001242314.2		c.-85-10837G>A		intron	N/A	NP_001229243.1
	MAP3K13	NM_001242317.2		c.39-25785G>A		intron	N/A	NP_001229246.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MAP3K13	ENST00000265026.8	TSL:1 MANE Select	c.-85-10837G>A		intron	N/A	ENSP00000265026.3
	MAP3K13	ENST00000424227.5	TSL:1	c.-85-10837G>A		intron	N/A	ENSP00000399910.1
	MAP3K13	ENST00000433092.5	TSL:1	n.-85-10837G>A		intron	N/A	ENSP00000389798.1

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

African (AFR) AF: 0.398 AC: 13302 AN: 33402

American (AMR) AF: 0.561 AC: 25086 AN: 44704

Ashkenazi Jewish (ASJ) AF: 0.714 AC: 18651 AN: 26126

East Asian (EAS) AF: 0.482 AC: 19127 AN: 39694

South Asian (SAS) AF: 0.536 AC: 46151 AN: 86162

European-Finnish (FIN) AF: 0.610 AC: 32564 AN: 53396

Middle Eastern (MID) AF: 0.648 AC: 2874 AN: 4434

European-Non Finnish (NFE) AF: 0.684 AC: 759726 AN: 1111462

Other (OTH) AF: 0.635 AC: 38214 AN: 60226

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

African (AFR) AF: 0.408 AC: 16892 AN: 41406

American (AMR) AF: 0.582 AC: 8871 AN: 15240

Ashkenazi Jewish (ASJ) AF: 0.707 AC: 2452 AN: 3468

East Asian (EAS) AF: 0.459 AC: 2363 AN: 5148

South Asian (SAS) AF: 0.514 AC: 2467 AN: 4802

European-Finnish (FIN) AF: 0.613 AC: 6453 AN: 10532

Middle Eastern (MID) AF: 0.656 AC: 193 AN: 294

European-Non Finnish (NFE) AF: 0.683 AC: 46410 AN: 67954

Other (OTH) AF: 0.621 AC: 1306 AN: 2104

Alfa AF: 0.630 Hom.: 6840

Bravo AF: 0.573

Asia WGS AF: 0.488 AC: 1695 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.67
CADD	Benign	8.8
DANN	Benign	0.90
PhyloP100		-0.51
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs13099317; hg19: chr3-185135448; COSMIC: COSV53984971;