3-185424069-C-T

Variant names:

• chr3-185424069-C-T
• rs7629245
• NM_004721.5:c.-85-4428C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_004721.5(MAP3K13):​c.-85-4428C>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
• Publications: 11 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=-0.83).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.241 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MAP3K13	NM_004721.5	MANE Select	c.-85-4428C>T		intron	N/A	NP_004712.1	O43283-1
	MAP3K13	NM_001242314.2		c.-85-4428C>T		intron	N/A	NP_001229243.1	O43283-1
	MAP3K13	NM_001242317.2		c.39-19376C>T		intron	N/A	NP_001229246.1	O43283-5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MAP3K13	ENST00000265026.8	TSL:1 MANE Select	c.-85-4428C>T		intron	N/A	ENSP00000265026.3	O43283-1
	MAP3K13	ENST00000424227.5	TSL:1	c.-85-4428C>T		intron	N/A	ENSP00000399910.1	O43283-1
	MAP3K13	ENST00000433092.5	TSL:1	n.-85-4428C>T		intron	N/A	ENSP00000389798.1	O43283-6

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

African (AFR) AF: 0.0347 AC: 1442 AN: 41506

American (AMR) AF: 0.149 AC: 2278 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.155 AC: 537 AN: 3468

East Asian (EAS) AF: 0.221 AC: 1146 AN: 5176

South Asian (SAS) AF: 0.253 AC: 1219 AN: 4816

European-Finnish (FIN) AF: 0.184 AC: 1949 AN: 10568

Middle Eastern (MID) AF: 0.143 AC: 42 AN: 294

European-Non Finnish (NFE) AF: 0.151 AC: 10239 AN: 67996

Other (OTH) AF: 0.134 AC: 282 AN: 2110

Alfa AF: 0.142 Hom.: 2831

Bravo AF: 0.116

Asia WGS AF: 0.206 AC: 719 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	4.9
DANN	Benign	0.70
PhyloP100		0.062
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: rs7629245; hg19: chr3-185141857;