rs5868032

Variant names:

• chr5-56882021-TCAACAACAACAACAA-T
• rs5868032
• NM_005921.2:c.2833_2847delACAACAACAACAACA

Your query was ambiguous. Multiple possible variants found:

• chr5-56882021-TCAACAACAACAACAA-T
• chr5-56882021-TCAACAACAACAACAA-TCAA
• chr5-56882021-TCAACAACAACAACAA-TCAACAA
• chr5-56882021-TCAACAACAACAACAA-TCAACAACAA
• chr5-56882021-TCAACAACAACAACAA-TCAACAACAACAA
• chr5-56882021-TCAACAACAACAACAA-TCAACAACAACAACAACAA
• chr5-56882021-TCAACAACAACAACAA-TCAACAACAACAACAACAACAA

Variant summary

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

The NM_005921.2(MAP3K1):​c.2833_2847delACAACAACAACAACA​(p.Thr945_Thr949del) variant causes a conservative inframe deletion change. It is difficult to determine the true allele frequency of this variant because it is of type DEL_BIG, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.0000066 (0 hom., cov: 0)
  • Exomes 𝑓: 7.0e-7 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: MAP3K1 NM_005921.2 conservative_inframe_deletion
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 6.55
• Publications: 23 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, Labcorp Genetics (formerly Invitae), G2P
• 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 0 ACMG points.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005921.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MAP3K1	NM_005921.2	MANE Select	c.2833_2847delACAACAACAACAACA	p.Thr945_Thr949del	conservative_inframe_deletion	Exon 14 of 20	NP_005912.1	Q13233

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MAP3K1	ENST00000399503.4	TSL:1 MANE Select	c.2833_2847delACAACAACAACAACA	p.Thr945_Thr949del	conservative_inframe_deletion	Exon 14 of 20	ENSP00000382423.3	Q13233
	MAP3K1	ENST00000872825.1		c.2827_2841delACAACAACAACAACA	p.Thr943_Thr947del	conservative_inframe_deletion	Exon 14 of 20	ENSP00000542884.1
	MAP3K1	ENST00000948659.1		c.2632_2646delACAACAACAACAACA	p.Thr878_Thr882del	conservative_inframe_deletion	Exon 13 of 19	ENSP00000618718.1

Frequencies

GnomAD3 genomes AF: 0.00000662 AC: 1 AN: 150946 Hom.: 0 Cov.: 0

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000660

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 7.04e-7 AC: 1 AN: 1421430 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 707624

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 32802

American (AMR) AF: 0.0000226 AC: 1 AN: 44156

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25526

East Asian (EAS) AF: 0.00 AC: 0 AN: 39396

South Asian (SAS) AF: 0.00 AC: 0 AN: 84488

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52274

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5658

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1078202

Other (OTH) AF: 0.00 AC: 0 AN: 58928

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome AF: 0.00000662 AC: 1 AN: 150946 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 73616

African (AFR) AF: 0.00 AC: 0 AN: 40946

American (AMR) AF: 0.0000660 AC: 1 AN: 15160

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3462

East Asian (EAS) AF: 0.00 AC: 0 AN: 5124

South Asian (SAS) AF: 0.00 AC: 0 AN: 4800

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10412

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 314

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 67750

Other (OTH) AF: 0.00 AC: 0 AN: 2076

Alfa AF: 0.00 Hom.: 4880

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		6.6
Mutation Taster		=161/39	polymorphism

Splicing

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

Other links and lift over

dbSNP: rs5868032; hg19: chr5-56177848;