rs3822625

Variant names:

• chr5-56882284-A-C
• rs3822625
• NM_005921.2:c.3084A>C

Your query was ambiguous. Multiple possible variants found:

• chr5-56882284-A-C
• chr5-56882284-A-G
• chr5-56882284-A-T

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_005921.2(MAP3K1):​c.3084A>C​(p.Gln1028His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. Q1028Q) has been classified as Benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: MAP3K1 NM_005921.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.39
• Publications: 0 publications found

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]

MAP3K1 Gene-Disease associations (from GenCC):

• 46,XY sex reversal 6

  Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: Ambry Genetics, G2P, Labcorp Genetics (formerly Invitae)
• breast cancer

  Inheritance: AD Classification: MODERATE Submitted by: G2P
• 46,XY complete gonadal dysgenesis

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• 46,XY partial gonadal dysgenesis

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Uncertain_significance. The variant received 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.3084A>C	p.Gln1028His	missense_variant	Exon 14 of 20	ENST00000399503.4	NP_005912.1
MAP3K1	XM_047417218.1	c.3084A>C	p.Gln1028His	missense_variant	Exon 14 of 18		XP_047273174.1
MAP3K1	XM_047417219.1	c.2673A>C	p.Gln891His	missense_variant	Exon 15 of 21		XP_047273175.1
MAP3K1	XM_047417220.1	c.2673A>C	p.Gln891His	missense_variant	Exon 15 of 21		XP_047273176.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MAP3K1	ENST00000399503.4	c.3084A>C	p.Gln1028His	missense_variant	Exon 14 of 20	1	NM_005921.2	ENSP00000382423.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 63

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Pathogenic	0.16	D
BayesDel_noAF	Uncertain	0.0
CADD	Benign	21
DANN	Uncertain	1.0
DEOGEN2	Benign	0.079	T
Eigen	Uncertain	0.37
Eigen_PC	Uncertain	0.34
FATHMM_MKL	Uncertain	0.84	D
LIST_S2	Benign	0.79	T
M_CAP	Benign	0.043	D
MetaRNN	Uncertain	0.56	D
MetaSVM	Uncertain	-0.20	T
MutationAssessor	Benign	2.0	M
PhyloP100		1.4
PrimateAI	Uncertain	0.51	T
PROVEAN	Benign	-0.51	N
REVEL	Uncertain	0.35
Sift	Pathogenic	0.0	D
Sift4G	Benign	0.31	T
Polyphen		1.0	D
Vest4		0.24
MutPred		0.11		Loss of MoRF binding (P = 0.1604);
MVP		0.82
MPC		0.22
ClinPred		0.82	D
GERP RS		3.7
Varity_R		0.37
gMVP		0.39
Mutation Taster		=63/37	polymorphism

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

Other links and lift over

dbSNP: rs3822625; hg19: chr5-56178111;