rs16997315

Positions:

• chrX-19483855-A-G

Variant summary

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

The NM_001001671.4(MAP3K15):​c.525+2627T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0217 in 111,945 control chromosomes in the GnomAD database, including 65 homozygotes. There are 694 hemizygotes in GnomAD. 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 0.022 (65 hom., 694 hem., cov: 23)
• Consequence: MAP3K15 NM_001001671.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0810

Genes affected

MAP3K15 (HGNC:31689): (mitogen-activated protein kinase kinase kinase 15) The protein encoded by this gene is a member of the mitogen-activated protein kinase (MAPK) family. These family members function in a protein kinase signal transduction cascade, where an activated MAPK kinase kinase (MAP3K) phosphorylates and activates a specific MAPK kinase (MAP2K), which then activates a specific MAPK. This MAP3K protein plays an essential role in apoptotic cell death triggered by cellular stresses. [provided by RefSeq, Jul 2010]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.072 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MAP3K15	NM_001001671.4	c.525+2627T>C		intron_variant		ENST00000338883.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MAP3K15	ENST00000338883.9	c.525+2627T>C		intron_variant		5	NM_001001671.4	P1

Frequencies

GnomAD3 genomes AF: 0.0217 AC: 2423 AN: 111891 Hom.: 64 Cov.: 23 AF XY: 0.0203 AC XY: 693 AN XY: 34065

Gnomad AFR AF: 0.0746

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00815

Gnomad ASJ AF: 0.00226

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000357

Gnomad OTH AF: 0.0166

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

GnomAD4 genome AF: 0.0217 AC: 2427 AN: 111945 Hom.: 65 Cov.: 23 AF XY: 0.0203 AC XY: 694 AN XY: 34129

Gnomad4 AFR AF: 0.0745

Gnomad4 AMR AF: 0.00814

Gnomad4 ASJ AF: 0.00226

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000357

Gnomad4 OTH AF: 0.0164

Alfa AF: 0.0214 Hom.: 78

Bravo AF: 0.0263

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	8.5
DANN	Benign	0.72

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: rs16997315; hg19: chrX-19501973;