rs560912060

Positions:

• chr1-154273375-AGATGAT-A
• chr1-154273375-AGATGAT-AGAT

Variant summary

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

The NM_006118.4(HAX1):​c.99_104del​(p.Asp33_Asp34del) variant causes a inframe deletion change. 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. D32D) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 31)
• Consequence: HAX1 NM_006118.4 inframe_deletion
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.38

Genes affected

HAX1 (HGNC:16915): (HCLS1 associated protein X-1) The protein encoded by this gene is known to associate with hematopoietic cell-specific Lyn substrate 1, a substrate of Src family tyrosine kinases. It also interacts with the product of the polycystic kidney disease 2 gene, mutations in which are associated with autosomal-dominant polycystic kidney disease, and with the F-actin-binding protein, cortactin. It was earlier thought that this gene product is mainly localized in the mitochondria, however, recent studies indicate it to be localized in the cell body. Mutations in this gene result in autosomal recessive severe congenital neutropenia, also known as Kostmann disease. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

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/exons	MANE	UniProt
HAX1	NM_006118.4	c.99_104del	p.Asp33_Asp34del	inframe_deletion	2/7	ENST00000328703.12
HAX1	NM_001018837.2	c.54-99_54-94del		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HAX1	ENST00000328703.12	c.99_104del	p.Asp33_Asp34del	inframe_deletion	2/7	1	NM_006118.4	P3

Frequencies

GnomAD3 genomes Cov.: 31

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Cov.: 31

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: rs560912060; hg19: chr1-154245851;