rs12632248

Variant names:

• chr3-185422125-G-A
• rs12632248
• NM_004721.5:c.-85-6372G>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.-85-6372G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0531 in 152,274 control chromosomes in the GnomAD database, including 351 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 0.053 (351 hom., cov: 32)
• Consequence: MAP3K13 NM_004721.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.642
• Publications: 7 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]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.215 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MAP3K13	NM_004721.5	c.-85-6372G>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.-85-6372G>A		intron_variant	Intron 1 of 13	1	NM_004721.5	ENSP00000265026.3

Frequencies

GnomAD3 genomes AF: 0.0531 AC: 8076 AN: 152154 Hom.: 351 Cov.: 32

Gnomad AFR AF: 0.0757

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0671

Gnomad ASJ AF: 0.0253

Gnomad EAS AF: 0.227

Gnomad SAS AF: 0.0731

Gnomad FIN AF: 0.0510

Gnomad MID AF: 0.0443

Gnomad NFE AF: 0.0245

Gnomad OTH AF: 0.0368

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

GnomAD4 genome AF: 0.0531 AC: 8081 AN: 152274 Hom.: 351 Cov.: 32 AF XY: 0.0563 AC XY: 4195 AN XY: 74456

African (AFR) AF: 0.0758 AC: 3147 AN: 41542

American (AMR) AF: 0.0671 AC: 1026 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.0253 AC: 88 AN: 3472

East Asian (EAS) AF: 0.226 AC: 1171 AN: 5182

South Asian (SAS) AF: 0.0730 AC: 352 AN: 4822

European-Finnish (FIN) AF: 0.0510 AC: 541 AN: 10612

Middle Eastern (MID) AF: 0.0374 AC: 11 AN: 294

European-Non Finnish (NFE) AF: 0.0245 AC: 1666 AN: 68030

Other (OTH) AF: 0.0374 AC: 79 AN: 2112

Alfa AF: 0.0343 Hom.: 644

Bravo AF: 0.0553

Asia WGS AF: 0.144 AC: 498 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	0.21
DANN	Benign	0.57
PhyloP100		-0.64
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: rs12632248; hg19: chr3-185139913;