chr2-134993279-T-C

Position:

• chr2-134993279-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.575-1699A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.295 in 152,068 control chromosomes in the GnomAD database, including 7,411 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 0.30 (7411 hom., cov: 32)
• Consequence: MAP3K19 NM_025052.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.30

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]

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 (EAS) allele frequency at 95% confidence interval = 0.538 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MAP3K19	NM_025052.5	c.575-1699A>G		intron_variant		ENST00000392915.7	NP_079328.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MAP3K19	ENST00000392915.7	c.575-1699A>G		intron_variant		5	NM_025052.5	ENSP00000376647	P2

Frequencies

GnomAD3 genomes AF: 0.295 AC: 44821 AN: 151948 Hom.: 7391 Cov.: 32

Gnomad AFR AF: 0.368

Gnomad AMI AF: 0.309

Gnomad AMR AF: 0.294

Gnomad ASJ AF: 0.464

Gnomad EAS AF: 0.554

Gnomad SAS AF: 0.387

Gnomad FIN AF: 0.253

Gnomad MID AF: 0.618

Gnomad NFE AF: 0.220

Gnomad OTH AF: 0.329

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

GnomAD4 genome AF: 0.295 AC: 44889 AN: 152068 Hom.: 7411 Cov.: 32 AF XY: 0.303 AC XY: 22537 AN XY: 74328

Gnomad4 AFR AF: 0.368

Gnomad4 AMR AF: 0.294

Gnomad4 ASJ AF: 0.464

Gnomad4 EAS AF: 0.555

Gnomad4 SAS AF: 0.385

Gnomad4 FIN AF: 0.253

Gnomad4 NFE AF: 0.220

Gnomad4 OTH AF: 0.331

Alfa AF: 0.268 Hom.: 765

Bravo AF: 0.301

Asia WGS AF: 0.458 AC: 1590 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	0.97
DANN	Benign	0.43

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: rs2322254; hg19: chr2-135750849;