rs9376230

Variant names:

• chr6-136781227-C-A
• rs9376230
• NM_005923.4:c.448+10483G>T

Your query was ambiguous. Multiple possible variants found:

• chr6-136781227-C-A
• chr6-136781227-C-G
• chr6-136781227-C-T

Variant summary

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

The NM_005923.4(MAP3K5):​c.448+10483G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.621 in 151,946 control chromosomes in the GnomAD database, including 29,383 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 0.62 (29383 hom., cov: 31)
• Consequence: MAP3K5 NM_005923.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0350
• Publications: 7 publications found

Genes affected

MAP3K5 (HGNC:6857): (mitogen-activated protein kinase kinase kinase 5) Mitogen-activated protein kinase (MAPK) signaling cascades include MAPK or extracellular signal-regulated kinase (ERK), MAPK kinase (MKK or MEK), and MAPK kinase kinase (MAPKKK or MEKK). MAPKK kinase/MEKK phosphorylates and activates its downstream protein kinase, MAPK kinase/MEK, which in turn activates MAPK. The kinases of these signaling cascades are highly conserved, and homologs exist in yeast, Drosophila, and mammalian cells. MAPKKK5 contains 1,374 amino acids with all 11 kinase subdomains. Northern blot analysis shows that MAPKKK5 transcript is abundantly expressed in human heart and pancreas. The MAPKKK5 protein phosphorylates and activates MKK4 (aliases SERK1, MAPKK4) in vitro, and activates c-Jun N-terminal kinase (JNK)/stress-activated protein kinase (SAPK) during transient expression in COS and 293 cells; MAPKKK5 does not activate MAPK/ERK. [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 (AMR) allele frequency at 95% confidence interval = 0.664 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MAP3K5	NM_005923.4	c.448+10483G>T		intron_variant	Intron 1 of 29	ENST00000359015.5	NP_005914.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MAP3K5	ENST00000359015.5	c.448+10483G>T		intron_variant	Intron 1 of 29	1	NM_005923.4	ENSP00000351908.4
MAP3K5	ENST00000698928.1	c.775+10483G>T		intron_variant	Intron 2 of 30			ENSP00000514039.1

Frequencies

GnomAD3 genomes AF: 0.621 AC: 94255 AN: 151828 Hom.: 29363 Cov.: 31

Gnomad AFR AF: 0.633

Gnomad AMI AF: 0.479

Gnomad AMR AF: 0.675

Gnomad ASJ AF: 0.656

Gnomad EAS AF: 0.535

Gnomad SAS AF: 0.561

Gnomad FIN AF: 0.560

Gnomad MID AF: 0.547

Gnomad NFE AF: 0.622

Gnomad OTH AF: 0.608

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

GnomAD4 genome AF: 0.621 AC: 94312 AN: 151946 Hom.: 29383 Cov.: 31 AF XY: 0.618 AC XY: 45885 AN XY: 74252

African (AFR) AF: 0.633 AC: 26204 AN: 41414

American (AMR) AF: 0.675 AC: 10305 AN: 15258

Ashkenazi Jewish (ASJ) AF: 0.656 AC: 2276 AN: 3470

East Asian (EAS) AF: 0.535 AC: 2758 AN: 5156

South Asian (SAS) AF: 0.560 AC: 2707 AN: 4830

European-Finnish (FIN) AF: 0.560 AC: 5901 AN: 10544

Middle Eastern (MID) AF: 0.541 AC: 159 AN: 294

European-Non Finnish (NFE) AF: 0.622 AC: 42286 AN: 67962

Other (OTH) AF: 0.607 AC: 1281 AN: 2110

Alfa AF: 0.619 Hom.: 47798

Bravo AF: 0.628

Asia WGS AF: 0.584 AC: 2031 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	8.1
DANN	Benign	0.74
PhyloP100		0.035
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: rs9376230; hg19: chr6-137102365;