5-56815617-C-A

Variant names:

• chr5-56815617-C-A
• NM_005921.2:c.44C>A

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_005921.2(MAP3K1):​c.44C>A​(p.Pro15Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000861 in 1,160,900 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 8.6e-7 (0 hom.)
• Consequence: MAP3K1 NM_005921.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.56

Genes affected

MAP3K1 (HGNC:6848): (mitogen-activated protein kinase kinase kinase 1) The protein encoded by this gene is a serine/threonine kinase and is part of some signal transduction cascades, including the ERK and JNK kinase pathways as well as the NF-kappa-B pathway. The encoded protein is activated by autophosphorylation and requires magnesium as a cofactor in phosphorylating other proteins. This protein has E3 ligase activity conferred by a plant homeodomain (PHD) in its N-terminus and phospho-kinase activity conferred by a kinase domain in its C-terminus. [provided by RefSeq, Mar 2012]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MAP3K1	NM_005921.2	c.44C>A	p.Pro15Gln	missense_variant	Exon 1 of 20	ENST00000399503.4	NP_005912.1
MAP3K1	XM_047417218.1	c.44C>A	p.Pro15Gln	missense_variant	Exon 1 of 18		XP_047273174.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MAP3K1	ENST00000399503.4	c.44C>A	p.Pro15Gln	missense_variant	Exon 1 of 20	1	NM_005921.2	ENSP00000382423.3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 8.61e-7 AC: 1 AN: 1160900 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 563282

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000104

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Uncertain	0.016	T
BayesDel_noAF	Benign	-0.22
CADD	Benign	23
DANN	Uncertain	0.99
DEOGEN2	Benign	0.084	T
Eigen	Benign	0.080
Eigen_PC	Benign	0.12
FATHMM_MKL	Benign	0.15	N
LIST_S2	Benign	0.52	T
M_CAP	Pathogenic	0.89	D
MetaRNN	Uncertain	0.45	T
MetaSVM	Benign	-0.82	T
MutationAssessor	Benign	0.55	N
PrimateAI	Pathogenic	0.92	D
PROVEAN	Benign	-0.35	N
REVEL	Benign	0.14
Sift	Uncertain	0.015	D
Sift4G	Benign	0.10	T
Polyphen		0.93	P
Vest4		0.51
MutPred		0.15		Gain of MoRF binding (P = 0.0287);
MVP		0.63
MPC		0.73
ClinPred		0.74	D
GERP RS		3.1
Varity_R		0.22
gMVP		0.17

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr5-56111444;