rs962786

Positions:

• chr1-233353308-T-G

Variant summary

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

The NM_032435.3(MAP3K21):​c.987-499T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.454 in 151,976 control chromosomes in the GnomAD database, including 16,134 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 0.45 (16134 hom., cov: 32)
• Consequence: MAP3K21 NM_032435.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.28

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=-0.9).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.551 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MAP3K21	NM_032435.3	c.987-499T>G		intron_variant		ENST00000366624.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MAP3K21	ENST00000366624.8	c.987-499T>G		intron_variant		1	NM_032435.3	P2
MAP3K21	ENST00000366623.7	c.987-499T>G		intron_variant		1		A2

Frequencies

GnomAD3 genomes AF: 0.453 AC: 68845 AN: 151858 Hom.: 16090 Cov.: 32

Gnomad AFR AF: 0.531

Gnomad AMI AF: 0.378

Gnomad AMR AF: 0.561

Gnomad ASJ AF: 0.351

Gnomad EAS AF: 0.524

Gnomad SAS AF: 0.467

Gnomad FIN AF: 0.383

Gnomad MID AF: 0.351

Gnomad NFE AF: 0.394

Gnomad OTH AF: 0.431

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

GnomAD4 genome AF: 0.454 AC: 68949 AN: 151976 Hom.: 16134 Cov.: 32 AF XY: 0.455 AC XY: 33788 AN XY: 74292

Gnomad4 AFR AF: 0.531

Gnomad4 AMR AF: 0.561

Gnomad4 ASJ AF: 0.351

Gnomad4 EAS AF: 0.524

Gnomad4 SAS AF: 0.468

Gnomad4 FIN AF: 0.383

Gnomad4 NFE AF: 0.394

Gnomad4 OTH AF: 0.435

Alfa AF: 0.455 Hom.: 2611

Bravo AF: 0.467

Asia WGS AF: 0.544 AC: 1894 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.56
DANN	Benign	0.70

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: rs962786; hg19: chr1-233489054;