rs5955762

Variant names:

• chrX-19372864-C-G
• rs5955762
• NM_001001671.4:c.2934-37G>C

Your query was ambiguous. Multiple possible variants found:

• chrX-19372864-C-G
• chrX-19372864-C-T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001001671.4(MAP3K15):​c.2934-37G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000188 in 1,066,265 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 1 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: not found (cov: 21)
  • Exomes 𝑓: 0.0000019 (0 hom. 1 hem.)
• Consequence: MAP3K15 NM_001001671.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.40
• Publications: 1 publications found

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

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001001671.4. 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
	MAP3K15	NM_001001671.4	MANE Select	c.2934-37G>C		intron	N/A	NP_001001671.3	Q6ZN16-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MAP3K15	ENST00000338883.9	TSL:5 MANE Select	c.2934-37G>C		intron	N/A	ENSP00000345629.4	Q6ZN16-1
	MAP3K15	ENST00000927253.1		c.2967-37G>C		intron	N/A	ENSP00000597312.1
	MAP3K15	ENST00000947404.1		c.2931-37G>C		intron	N/A	ENSP00000617463.1

Frequencies

GnomAD3 genomes Cov.: 21

GnomAD2 exomes AF: 0.00000614 AC: 1 AN: 162893 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000138

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000188 AC: 2 AN: 1066265 Hom.: 0 Cov.: 27 AF XY: 0.00000296 AC XY: 1 AN XY: 337947

African (AFR) AF: 0.00 AC: 0 AN: 25953

American (AMR) AF: 0.00 AC: 0 AN: 33876

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 17846

East Asian (EAS) AF: 0.00 AC: 0 AN: 29899

South Asian (SAS) AF: 0.00 AC: 0 AN: 50235

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 39639

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4009

European-Non Finnish (NFE) AF: 0.00000244 AC: 2 AN: 819933

Other (OTH) AF: 0.00 AC: 0 AN: 44875

GnomAD4 genome Cov.: 21

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	0.26
DANN	Benign	0.49
PhyloP100		-1.4

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs5955762;

hg19: chrX-19390982;