X-19372864-C-T

Position:

• chrX-19372864-C-T

Variant summary

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

The NM_001001671.4(MAP3K15):​c.2934-37G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0458 in 1,176,859 control chromosomes in the GnomAD database, including 2,769 homozygotes. There are 17,528 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 0.11 (1172 hom., 3211 hem., cov: 21)
  • Exomes 𝑓: 0.039 (1597 hom. 14317 hem.)
• Consequence: MAP3K15 NM_001001671.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.40

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=-0.85).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.305 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MAP3K15	NM_001001671.4	c.2934-37G>A		intron_variant		ENST00000338883.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MAP3K15	ENST00000338883.9	c.2934-37G>A		intron_variant		5	NM_001001671.4	P1
MAP3K15	ENST00000470101.1	n.315G>A		non_coding_transcript_exon_variant	1/8	2
MAP3K15	ENST00000359173.7	c.*1411-37G>A		intron_variant, NMD_transcript_variant		2
MAP3K15	ENST00000518578.5	n.2996-37G>A		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.108 AC: 11894 AN: 110595 Hom.: 1171 Cov.: 21 AF XY: 0.0973 AC XY: 3200 AN XY: 32893

Gnomad AFR AF: 0.311

Gnomad AMI AF: 0.111

Gnomad AMR AF: 0.0451

Gnomad ASJ AF: 0.0734

Gnomad EAS AF: 0.00490

Gnomad SAS AF: 0.120

Gnomad FIN AF: 0.0189

Gnomad MID AF: 0.131

Gnomad NFE AF: 0.0225

Gnomad OTH AF: 0.0947

GnomAD3 exomes AF: 0.0588 AC: 9570 AN: 162893 Hom.: 629 AF XY: 0.0567 AC XY: 2997 AN XY: 52873

Gnomad AFR exome AF: 0.321

Gnomad AMR exome AF: 0.0262

Gnomad ASJ exome AF: 0.0732

Gnomad EAS exome AF: 0.00291

Gnomad SAS exome AF: 0.138

Gnomad FIN exome AF: 0.0232

Gnomad NFE exome AF: 0.0252

Gnomad OTH exome AF: 0.0475

GnomAD4 exome AF: 0.0394 AC: 41991 AN: 1066215 Hom.: 1597 Cov.: 27 AF XY: 0.0424 AC XY: 14317 AN XY: 337937

Gnomad4 AFR exome AF: 0.326

Gnomad4 AMR exome AF: 0.0307

Gnomad4 ASJ exome AF: 0.0715

Gnomad4 EAS exome AF: 0.00478

Gnomad4 SAS exome AF: 0.141

Gnomad4 FIN exome AF: 0.0245

Gnomad4 NFE exome AF: 0.0246

Gnomad4 OTH exome AF: 0.0544

GnomAD4 genome AF: 0.108 AC: 11906 AN: 110644 Hom.: 1172 Cov.: 21 AF XY: 0.0974 AC XY: 3211 AN XY: 32952

Gnomad4 AFR AF: 0.310

Gnomad4 AMR AF: 0.0451

Gnomad4 ASJ AF: 0.0734

Gnomad4 EAS AF: 0.00491

Gnomad4 SAS AF: 0.121

Gnomad4 FIN AF: 0.0189

Gnomad4 NFE AF: 0.0225

Gnomad4 OTH AF: 0.0935

Alfa AF: 0.0741 Hom.: 693

Bravo AF: 0.121

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	0.30
DANN	Benign	0.76

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: rs5955762; hg19: chrX-19390982;