1-154272666-TC-T

Variant names:

• chr1-154272666-TC-T
• rs373592376
• NM_006118.4:c.-53delC

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BS1 BS2

The NM_006118.4(HAX1):​c.-53delC variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00233 in 1,556,954 control chromosomes in the GnomAD database, including 100 homozygotes. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0014 (7 hom., cov: 32)
  • Exomes 𝑓: 0.0024 (93 hom.)
• Consequence: HAX1 NM_006118.4 5_prime_UTR
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.0410

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 Benign. Variant got -10 ACMG points.

• BP6: Variant 1-154272666-TC-T is Benign according to our data. Variant chr1-154272666-TC-T is described in ClinVar as [Likely_benign]. Clinvar id is 292701.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.00138 (210/152210) while in subpopulation SAS AF= 0.0412 (199/4830). AF 95% confidence interval is 0.0365. There are 7 homozygotes in gnomad4. There are 153 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 7 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HAX1	NM_006118.4	c.-53delC		5_prime_UTR_variant	Exon 1 of 7	ENST00000328703.12	NP_006109.2
HAX1	NM_001018837.2	c.-53delC		5_prime_UTR_variant	Exon 1 of 7		NP_001018238.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HAX1	ENST00000328703	c.-53delC		5_prime_UTR_variant	Exon 1 of 7	1	NM_006118.4	ENSP00000329002.7

Frequencies

GnomAD3 genomes AF: 0.00139 AC: 211 AN: 152092 Hom.: 7 Cov.: 32

Gnomad AFR AF: 0.000145

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.0414

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.00191

GnomAD4 exome AF: 0.00243 AC: 3414 AN: 1404744 Hom.: 93 Cov.: 26 AF XY: 0.00355 AC XY: 2493 AN XY: 701832

Gnomad4 AFR exome AF: 0.000154

Gnomad4 AMR exome AF: 0.0000452

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000762

Gnomad4 SAS exome AF: 0.0375

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000556

Gnomad4 OTH exome AF: 0.00272

GnomAD4 genome AF: 0.00138 AC: 210 AN: 152210 Hom.: 7 Cov.: 32 AF XY: 0.00206 AC XY: 153 AN XY: 74406

Gnomad4 AFR AF: 0.000144

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.0412

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000147

Gnomad4 OTH AF: 0.00189

Alfa AF: 0.000174 Hom.: 0

Bravo AF: 0.000264

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Severe congenital neutropenia Benign:1

Jun 14, 2016

Illumina Laboratory Services, Illumina

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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Computational scores

Source: dbNSFP v4.3

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs373592376; hg19: chr1-154245142;