rs58142675

Variant names:

• chr17-63632869-G-A
• rs58142675
• NM_002401.5:c.126+67G>A

Your query was ambiguous. Multiple possible variants found:

• chr17-63632869-G-A
• chr17-63632869-G-T

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_Strong BS2

The NM_002401.5(MAP3K3):​c.126+67G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00002 in 1,597,962 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 0.000026 (0 hom., cov: 31)
  • Exomes 𝑓: 0.000019 (0 hom.)
• Consequence: MAP3K3 NM_002401.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.802

Genes affected

MAP3K3 (HGNC:6855): (mitogen-activated protein kinase kinase kinase 3) This gene product is a 626-amino acid polypeptide that is 96.5% identical to mouse Mekk3. Its catalytic domain is closely related to those of several other kinases, including mouse Mekk2, tobacco NPK, and yeast Ste11. Northern blot analysis revealed a 4.6-kb transcript that appears to be ubiquitously expressed. This protein directly regulates the stress-activated protein kinase (SAPK) and extracellular signal-regulated protein kinase (ERK) pathways by activating SEK and MEK1/2 respectively; it does not regulate the p38 pathway. In cotransfection assays, it enhanced transcription from a nuclear factor kappa-B (NFKB)-dependent reporter gene, consistent with a role in the SAPK pathway. Alternatively spliced transcript variants encoding distinct isoforms have been observed. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -8 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.72).
• BS2: High AC in GnomAdExome4 at 28 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MAP3K3	NM_002401.5	c.126+67G>A		intron_variant	Intron 2 of 15	ENST00000361733.8	NP_002392.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MAP3K3	ENST00000361733.8	c.126+67G>A		intron_variant	Intron 2 of 15	1	NM_002401.5	ENSP00000354485.4

Frequencies

GnomAD3 genomes AF: 0.0000197 AC: 3 AN: 152120 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.0000241

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000192

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.0000194 AC: 28 AN: 1445724 Hom.: 0 AF XY: 0.0000181 AC XY: 13 AN XY: 719098

Gnomad4 AFR exome AF: 0.0000907

Gnomad4 AMR exome AF: 0.0000228

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.000177

Gnomad4 SAS exome AF: 0.0000118

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000109

Gnomad4 OTH exome AF: 0.0000670

GnomAD4 genome AF: 0.0000263 AC: 4 AN: 152238 Hom.: 0 Cov.: 31 AF XY: 0.0000403 AC XY: 3 AN XY: 74442

Gnomad4 AFR AF: 0.0000482

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000147

Gnomad4 OTH AF: 0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.72
CADD	Benign	14
DANN	Benign	0.58

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: rs58142675; hg19: chr17-61710229;