rs16858997

Positions:

• chr1-233369427-G-A
• chr1-233369427-G-C

Variant summary

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

The NM_032435.3(MAP3K21):​c.1553-2611G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.344 in 151,834 control chromosomes in the GnomAD database, including 9,466 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 0.34 (9466 hom., cov: 31)
• Consequence: MAP3K21 NM_032435.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.283

Genes affected

MAP3K21 (HGNC:29798): (mitogen-activated protein kinase kinase kinase 21) Predicted to enable protein homodimerization activity and protein kinase activity. Predicted to be involved in protein autophosphorylation and signal transduction. Predicted to be active in cytoplasm. [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=-0.95).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.496 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MAP3K21	NM_032435.3	c.1553-2611G>A		intron_variant		ENST00000366624.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MAP3K21	ENST00000366624.8	c.1553-2611G>A		intron_variant		1	NM_032435.3	P2
MAP3K21	ENST00000366623.7	c.1553-2611G>A		intron_variant		1		A2

Frequencies

GnomAD3 genomes AF: 0.343 AC: 52111 AN: 151714 Hom.: 9437 Cov.: 31

Gnomad AFR AF: 0.263

Gnomad AMI AF: 0.361

Gnomad AMR AF: 0.482

Gnomad ASJ AF: 0.290

Gnomad EAS AF: 0.511

Gnomad SAS AF: 0.457

Gnomad FIN AF: 0.344

Gnomad MID AF: 0.291

Gnomad NFE AF: 0.344

Gnomad OTH AF: 0.334

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

GnomAD4 genome AF: 0.344 AC: 52187 AN: 151834 Hom.: 9466 Cov.: 31 AF XY: 0.349 AC XY: 25875 AN XY: 74190

Gnomad4 AFR AF: 0.263

Gnomad4 AMR AF: 0.483

Gnomad4 ASJ AF: 0.290

Gnomad4 EAS AF: 0.512

Gnomad4 SAS AF: 0.458

Gnomad4 FIN AF: 0.344

Gnomad4 NFE AF: 0.344

Gnomad4 OTH AF: 0.340

Alfa AF: 0.351 Hom.: 9798

Bravo AF: 0.347

Asia WGS AF: 0.507 AC: 1763 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.52
DANN	Benign	0.38

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: rs16858997; hg19: chr1-233505173;