rs1663941517

Variant names:

• chr1-233382679-A-C
• rs1663941517
• NM_032435.3:c.3079A>C

Your query was ambiguous. Multiple possible variants found:

• chr1-233382679-A-C
• chr1-233382679-A-G

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_032435.3(MAP3K21):​c.3079A>C​(p.Ile1027Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/19 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. I1027V) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: MAP3K21 NM_032435.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.20

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 Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.05055815).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MAP3K21	NM_032435.3	c.3079A>C	p.Ile1027Leu	missense_variant	Exon 10 of 10	ENST00000366624.8	NP_115811.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MAP3K21	ENST00000366624.8	c.3079A>C	p.Ile1027Leu	missense_variant	Exon 10 of 10	1	NM_032435.3	ENSP00000355583.3
MAP3K21	ENST00000366622.1	c.1417A>C	p.Ile473Leu	missense_variant	Exon 4 of 4	1		ENSP00000355581.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.073
BayesDel_addAF	Benign	-0.18	T
BayesDel_noAF	Benign	-0.50
CADD	Benign	9.0
DANN	Benign	0.90
DEOGEN2	Benign	0.017	T;.
Eigen	Benign	-0.72
Eigen_PC	Benign	-0.65
FATHMM_MKL	Benign	0.43	N
LIST_S2	Benign	0.46	T;T
M_CAP	Benign	0.014	T
MetaRNN	Benign	0.051	T;T
MetaSVM	Benign	-0.99	T
PrimateAI	Benign	0.25	T
PROVEAN	Benign	-0.77	N;N
REVEL	Benign	0.024
Sift	Benign	0.35	T;T
Sift4G	Benign	0.38	T;T
Polyphen		0.0010	B;.
Vest4		0.054
MutPred		0.25		Loss of helix (P = 0.079);.;
MVP		0.24
MPC		0.11
ClinPred		0.18	T
GERP RS		2.4
Varity_R		0.045
gMVP		0.20

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: rs1663941517; hg19: chr1-233518425;