chr6-36138880-T-G

Position:

• chr6-36138880-T-G

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

The ENST00000373766.9(MAPK13):​c.691T>G​(p.Cys231Gly) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00234 in 1,610,656 control chromosomes in the GnomAD database, including 9 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/16 in silico tools predict 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 Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0025 (2 hom., cov: 32)
  • Exomes 𝑓: 0.0023 (7 hom.)
• Consequence: MAPK13 ENST00000373766.9 missense, splice_region
• Scores: Splicing: ADA: 0.0002903
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -4.18

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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0040469766).
• BP6: Variant 6-36138880-T-G is Benign according to our data. Variant chr6-36138880-T-G is described in ClinVar as [Likely_benign]. Clinvar id is 2656513.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Homozygotes in GnomAd4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MAPK13	NM_002754.5	c.843T>G	p.Ala281=	splice_region_variant, synonymous_variant	11/12	ENST00000211287.9	NP_002745.1
MAPK13	NR_072996.2	n.761T>G		splice_region_variant, non_coding_transcript_exon_variant	9/10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MAPK13	ENST00000373766.9	c.691T>G	p.Cys231Gly	missense_variant, splice_region_variant	9/10	1		ENSP00000362871
MAPK13	ENST00000211287.9	c.843T>G	p.Ala281=	splice_region_variant, synonymous_variant	11/12	1	NM_002754.5	ENSP00000211287	P1
MAPK13	ENST00000373759.1	c.*96T>G		3_prime_UTR_variant	8/8	5		ENSP00000362864

Frequencies

GnomAD3 genomes AF: 0.00250 AC: 381 AN: 152214 Hom.: 2 Cov.: 32

Gnomad AFR AF: 0.000313

Gnomad AMI AF: 0.0230

Gnomad AMR AF: 0.000916

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.0137

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00268

Gnomad OTH AF: 0.00191

GnomAD3 exomes AF: 0.00237 AC: 586 AN: 247730 Hom.: 2 AF XY: 0.00235 AC XY: 315 AN XY: 134000

Gnomad AFR exome AF: 0.000309

Gnomad AMR exome AF: 0.000979

Gnomad ASJ exome AF: 0.000103

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000297

Gnomad FIN exome AF: 0.0118

Gnomad NFE exome AF: 0.00246

Gnomad OTH exome AF: 0.00166

GnomAD4 exome AF: 0.00232 AC: 3388 AN: 1458324 Hom.: 7 Cov.: 32 AF XY: 0.00231 AC XY: 1673 AN XY: 725330

Gnomad4 AFR exome AF: 0.000391

Gnomad4 AMR exome AF: 0.000841

Gnomad4 ASJ exome AF: 0.000155

Gnomad4 EAS exome AF: 0.0000504

Gnomad4 SAS exome AF: 0.000395

Gnomad4 FIN exome AF: 0.00982

Gnomad4 NFE exome AF: 0.00240

Gnomad4 OTH exome AF: 0.00178

GnomAD4 genome AF: 0.00250 AC: 381 AN: 152332 Hom.: 2 Cov.: 32 AF XY: 0.00275 AC XY: 205 AN XY: 74484

Gnomad4 AFR AF: 0.000313

Gnomad4 AMR AF: 0.000915

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000207

Gnomad4 FIN AF: 0.0137

Gnomad4 NFE AF: 0.00268

Gnomad4 OTH AF: 0.00189

Alfa AF: 0.00227 Hom.: 2

Bravo AF: 0.00168

TwinsUK AF: 0.00162 AC: 6

ALSPAC AF: 0.00182 AC: 7

ESP6500AA AF: 0.000908 AC: 4

ESP6500EA AF: 0.00267 AC: 23

ExAC AF: 0.00185 AC: 224

EpiCase AF: 0.00234

EpiControl AF: 0.00255

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Aug 01, 2022

MAPK13: BP4, BP7 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Benign	-0.32	T
BayesDel_noAF	Benign	-0.24
CADD	Benign	0.40
DANN	Benign	0.43
Eigen	Benign	-0.79
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.039	N
LIST_S2	Benign	0.20	T
MetaRNN	Benign	0.0040	T
MetaSVM	Benign	-0.84	T
MutationTaster	Benign	1.0	D;D;D;N
PROVEAN	Benign	-0.14	N
REVEL	Benign	0.057
Sift	Pathogenic	0.0	D
Sift4G	Uncertain	0.041	D
Vest4		0.23
MVP		0.35
ClinPred		0.013	T
GERP RS		-9.4

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.00029
dbscSNV1_RF	Benign	0.040
SpliceAI score (max)		0.020		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: rs150922772; hg19: chr6-36106657;