X-55009198-ATA-T

Position:

• chrX-55009198-ATA-T

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PVS1_Moderate PM2

The NM_000032.5(ALAS2):​c.1744_1746delinsA​(p.Tyr582SerfsTer37) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 22)
• Consequence: ALAS2 NM_000032.5 frameshift
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.32

Genes affected

ALAS2 (HGNC:397): (5'-aminolevulinate synthase 2) The product of this gene specifies an erythroid-specific mitochondrially located enzyme. The encoded protein catalyzes the first step in the heme biosynthetic pathway. Defects in this gene cause X-linked pyridoxine-responsive sideroblastic anemia. Alternatively spliced transcript variants encoding different isoforms have been identified. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Uncertain_significance. Variant got 4 ACMG points.

• PVS1: Loss of function variant, product does not undergo nonsense mediated mRNA decay. Variant is located in the 3'-most exon, not predicted to undergo nonsense mediated mRNA decay. Fraction of 0.0113 CDS is truncated, and there are 0 pathogenic variants in the truncated region.
• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ALAS2	NM_000032.5	c.1744_1746delinsA	p.Tyr582SerfsTer37	frameshift_variant	11/11	ENST00000650242.1	NP_000023.2
ALAS2	NM_001037967.4	c.1633_1635delinsA	p.Tyr545SerfsTer37	frameshift_variant	10/10		NP_001033056.1
ALAS2	NM_001037968.4	c.1705_1707delinsA	p.Tyr569SerfsTer37	frameshift_variant	11/11		NP_001033057.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ALAS2	ENST00000650242.1	c.1744_1746delinsA	p.Tyr582SerfsTer37	frameshift_variant	11/11		NM_000032.5	ENSP00000497236	P1
ALAS2	ENST00000335854.8	c.1633_1635delinsA	p.Tyr545SerfsTer?	frameshift_variant	10/10	2		ENSP00000337131
ALAS2	ENST00000396198.7	c.1705_1707delinsA	p.Tyr569SerfsTer37	frameshift_variant	11/11	5		ENSP00000379501
ALAS2	ENST00000498636.1	c.*42_*44delinsA		3_prime_UTR_variant	5/5	3		ENSP00000495662

Frequencies

GnomAD3 genomes Cov.: 22

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

GnomAD4 genome Cov.: 22

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Revvity Omics, Revvity

Feb 10, 2023

- -

Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chrX-55035631;