rs1294255

Variant names:

• chr1-233365612-G-C
• rs1294255
• NM_032435.3:c.1552+3319G>C

Variant summary

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

The NM_032435.3(MAP3K21):​c.1552+3319G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.338 in 152,008 control chromosomes in the GnomAD database, including 9,598 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 (9598 hom., cov: 32)
• Consequence: MAP3K21 NM_032435.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.531

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 (EAS) allele frequency at 95% confidence interval = 0.415 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MAP3K21	NM_032435.3	c.1552+3319G>C		intron_variant	Intron 5 of 9	ENST00000366624.8	NP_115811.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MAP3K21	ENST00000366624.8	c.1552+3319G>C		intron_variant	Intron 5 of 9	1	NM_032435.3	ENSP00000355583.3
MAP3K21	ENST00000366623.7	c.1552+3319G>C		intron_variant	Intron 5 of 5	1		ENSP00000355582.3

Frequencies

GnomAD3 genomes AF: 0.338 AC: 51379 AN: 151890 Hom.: 9606 Cov.: 32

Gnomad AFR AF: 0.188

Gnomad AMI AF: 0.397

Gnomad AMR AF: 0.269

Gnomad ASJ AF: 0.363

Gnomad EAS AF: 0.422

Gnomad SAS AF: 0.337

Gnomad FIN AF: 0.451

Gnomad MID AF: 0.405

Gnomad NFE AF: 0.419

Gnomad OTH AF: 0.337

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

GnomAD4 genome AF: 0.338 AC: 51368 AN: 152008 Hom.: 9598 Cov.: 32 AF XY: 0.340 AC XY: 25237 AN XY: 74278

Gnomad4 AFR AF: 0.188

Gnomad4 AMR AF: 0.268

Gnomad4 ASJ AF: 0.363

Gnomad4 EAS AF: 0.421

Gnomad4 SAS AF: 0.336

Gnomad4 FIN AF: 0.451

Gnomad4 NFE AF: 0.419

Gnomad4 OTH AF: 0.334

Alfa AF: 0.374 Hom.: 1559

Bravo AF: 0.318

Asia WGS AF: 0.335 AC: 1162 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	2.2
DANN	Benign	0.55

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: rs1294255; hg19: chr1-233501358;