2-135030072-T-C

Position:

• chr2-135030072-T-C

Variant summary

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

The NM_025052.5(MAP3K19):​c.-95+240A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.266 in 152,086 control chromosomes in the GnomAD database, including 7,235 homozygotes. 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 0.27 (7235 hom., cov: 32)
• Consequence: MAP3K19 NM_025052.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.59

Genes affected

MAP3K19 (HGNC:26249): (mitogen-activated protein kinase kinase kinase 19) Predicted to enable ATP binding activity; protein serine kinase activity; and protein serine/threonine kinase activity. Predicted to be involved in protein phosphorylation. [provided by Alliance of Genome Resources, Apr 2022]

MAP3K19 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.48 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MAP3K19	NM_025052.5	c.-95+240A>G		intron_variant		ENST00000392915.7	NP_079328.3
MAP3K19	NM_001400438.1	c.-95+240A>G		intron_variant			NP_001387367.1
MAP3K19	XM_017005004.3	c.-63+240A>G		intron_variant			XP_016860493.1
MAP3K19	XM_017005005.3	c.-62-8242A>G		intron_variant			XP_016860494.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MAP3K19	ENST00000392915.7	c.-95+240A>G		intron_variant		5	NM_025052.5	ENSP00000376647.2

Frequencies

GnomAD3 genomes AF: 0.265 AC: 40307 AN: 151968 Hom.: 7204 Cov.: 32

Gnomad AFR AF: 0.485

Gnomad AMI AF: 0.0815

Gnomad AMR AF: 0.311

Gnomad ASJ AF: 0.245

Gnomad EAS AF: 0.305

Gnomad SAS AF: 0.382

Gnomad FIN AF: 0.137

Gnomad MID AF: 0.241

Gnomad NFE AF: 0.134

Gnomad OTH AF: 0.270

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

GnomAD4 genome AF: 0.266 AC: 40391 AN: 152086 Hom.: 7235 Cov.: 32 AF XY: 0.270 AC XY: 20065 AN XY: 74384

Gnomad4 AFR AF: 0.486

Gnomad4 AMR AF: 0.310

Gnomad4 ASJ AF: 0.245

Gnomad4 EAS AF: 0.305

Gnomad4 SAS AF: 0.381

Gnomad4 FIN AF: 0.137

Gnomad4 NFE AF: 0.134

Gnomad4 OTH AF: 0.270

Alfa AF: 0.188 Hom.: 971

Bravo AF: 0.284

Asia WGS AF: 0.354 AC: 1230 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.40
DANN	Benign	0.39

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs1551497; hg19: chr2-135787642;