chr5-56882021-TCAACAACAA-T

Position:

• chr5-56882021-TCAACAACAA-T

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2

The NM_005921.2(MAP3K1):​c.2839_2847delACAACAACA​(p.Thr947_Thr949del) variant causes a conservative inframe deletion change. The variant allele was found at a frequency of 0.0000585 in 1,572,462 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: 𝑓 0.000040 (0 hom., cov: 0)
  • Exomes 𝑓: 0.000061 (0 hom.)
• Consequence: MAP3K1 NM_005921.2 conservative_inframe_deletion
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 6.55

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 Likely_benign. Variant got -4 ACMG points.

• BS2: High AC in GnomAd4 at 6 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MAP3K1	NM_005921.2	c.2839_2847delACAACAACA	p.Thr947_Thr949del	conservative_inframe_deletion	14/20	ENST00000399503.4	NP_005912.1
MAP3K1	XM_047417218.1	c.2839_2847delACAACAACA	p.Thr947_Thr949del	conservative_inframe_deletion	14/18		XP_047273174.1
MAP3K1	XM_047417219.1	c.2428_2436delACAACAACA	p.Thr810_Thr812del	conservative_inframe_deletion	15/21		XP_047273175.1
MAP3K1	XM_047417220.1	c.2428_2436delACAACAACA	p.Thr810_Thr812del	conservative_inframe_deletion	15/21		XP_047273176.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MAP3K1	ENST00000399503.4	c.2839_2847delACAACAACA	p.Thr947_Thr949del	conservative_inframe_deletion	14/20	1	NM_005921.2	ENSP00000382423.3

Frequencies

GnomAD3 genomes AF: 0.0000397 AC: 6 AN: 150946 Hom.: 0 Cov.: 0

Gnomad AFR AF: 0.0000244

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000390

Gnomad SAS AF: 0.000208

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000295

Gnomad OTH AF: 0.00

GnomAD3 exomes AF: 0.000100 AC: 23 AN: 229430 Hom.: 0 AF XY: 0.000105 AC XY: 13 AN XY: 123974

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000923

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000293

Gnomad SAS exome AF: 0.000179

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000971

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000605 AC: 86 AN: 1421398 Hom.: 0 AF XY: 0.0000622 AC XY: 44 AN XY: 707612

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.0000679

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.000178

Gnomad4 SAS exome AF: 0.000154

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000529

Gnomad4 OTH exome AF: 0.0000849

GnomAD4 genome AF: 0.0000397 AC: 6 AN: 151064 Hom.: 0 Cov.: 0 AF XY: 0.0000407 AC XY: 3 AN XY: 73744

Gnomad4 AFR AF: 0.0000243

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.000391

Gnomad4 SAS AF: 0.000209

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000295

Gnomad4 OTH AF: 0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs5868032; hg19: chr5-56177848;