6-36136653-T-C

Position:

• chr6-36136653-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Moderate BP6_Moderate BS1 BS2

The NM_002754.5(MAPK13):​c.496-3T>C variant causes a splice region, splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00254 in 1,613,492 control chromosomes in the GnomAD database, including 82 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.012 (37 hom., cov: 33)
  • Exomes 𝑓: 0.0015 (45 hom.)
• Consequence: MAPK13 NM_002754.5 splice_region, splice_polypyrimidine_tract, intron
• Scores: Splicing: ADA: 0.00009058
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.706

Genes affected

MAPK13 (HGNC:6875): (mitogen-activated protein kinase 13) This gene encodes a member of the mitogen-activated protein (MAP) kinase family. MAP kinases act as an integration point for multiple biochemical signals, and are involved in a wide variety of cellular processes such as proliferation, differentiation, transcription regulation and development. The encoded protein is a p38 MAP kinase and is activated by proinflammatory cytokines and cellular stress. Substrates of the encoded protein include the transcription factor ATF2 and the microtubule dynamics regulator stathmin. Alternatively spliced transcript variants have been observed for this gene. [provided by RefSeq, Jul 2012]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.34).
• BP6: Variant 6-36136653-T-C is Benign according to our data. Variant chr6-36136653-T-C is described in ClinVar as [Benign]. Clinvar id is 789745.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0123 (1873/152314) while in subpopulation AFR AF= 0.0414 (1720/41574). AF 95% confidence interval is 0.0397. There are 37 homozygotes in gnomad4. There are 885 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 37 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MAPK13	NM_002754.5	c.496-3T>C		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		ENST00000211287.9	NP_002745.1
MAPK13	NR_072996.2	n.566-3T>C		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MAPK13	ENST00000211287.9	c.496-3T>C		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		1	NM_002754.5	ENSP00000211287	P1
MAPK13	ENST00000373766.9	c.496-3T>C		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		1		ENSP00000362871
MAPK13	ENST00000373759.1	c.262-3T>C		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		5		ENSP00000362864

Frequencies

GnomAD3 genomes AF: 0.0122 AC: 1858 AN: 152196 Hom.: 36 Cov.: 33

Gnomad AFR AF: 0.0411

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00759

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000622

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000235

Gnomad OTH AF: 0.00908

GnomAD3 exomes AF: 0.00341 AC: 850 AN: 249194 Hom.: 12 AF XY: 0.00260 AC XY: 350 AN XY: 134806

Gnomad AFR exome AF: 0.0428

Gnomad AMR exome AF: 0.00329

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000547

Gnomad SAS exome AF: 0.000164

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000338

Gnomad OTH exome AF: 0.00148

GnomAD4 exome AF: 0.00152 AC: 2223 AN: 1461178 Hom.: 45 Cov.: 32 AF XY: 0.00136 AC XY: 990 AN XY: 726838

Gnomad4 AFR exome AF: 0.0464

Gnomad4 AMR exome AF: 0.00365

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000252

Gnomad4 SAS exome AF: 0.000371

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000184

Gnomad4 OTH exome AF: 0.00391

GnomAD4 genome AF: 0.0123 AC: 1873 AN: 152314 Hom.: 37 Cov.: 33 AF XY: 0.0119 AC XY: 885 AN XY: 74472

Gnomad4 AFR AF: 0.0414

Gnomad4 AMR AF: 0.00758

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000415

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000235

Gnomad4 OTH AF: 0.00899

Alfa AF: 0.00608 Hom.: 8

Bravo AF: 0.0145

Asia WGS AF: 0.00404 AC: 14 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Dec 31, 2019

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.34
CADD	Benign	9.6
DANN	Benign	0.90

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000091
dbscSNV1_RF	Benign	0.010
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: rs55732669; hg19: chr6-36104430;