rs12632248

chr3-185422125-G-A

Variant summary

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

The NM_004721.5(MAP3K13):c.-85-6372G>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

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=-0.85).
• 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/exons	MANE	UniProt
MAP3K13	NM_004721.5	c.-85-6372G>A		intron_variant		ENST00000265026.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MAP3K13	ENST00000265026.8	c.-85-6372G>A		intron_variant		1	NM_004721.5	P1

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

Gnomad4 AFR AF: 0.0758

Gnomad4 AMR AF: 0.0671

Gnomad4 ASJ AF: 0.0253

Gnomad4 EAS AF: 0.226

Gnomad4 SAS AF: 0.0730

Gnomad4 FIN AF: 0.0510

Gnomad4 NFE AF: 0.0245

Gnomad4 OTH AF: 0.0374

Alfa AF: 0.0301 Hom.: 203

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

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: rs12632248; hg19: chr3-185139913;