X-55013523-G-C

Variant names:

• chrX-55013523-G-C
• NM_000032.5:c.1563C>G

Variant summary

Our verdict is Likely benign. Variant got -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP7

The NM_000032.5(ALAS2):​c.1563C>G​(p.Ser521Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000455 in 1,097,899 control chromosomes in the GnomAD database, with no homozygous occurrence. There are no hemizygote samples in GnomAD. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 23)
  • Exomes 𝑓: 0.0000046 (0 hom. 0 hem.)
• Consequence: ALAS2 NM_000032.5 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.191

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 Likely_benign. Variant got -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.58).
• BP7: Synonymous conserved (PhyloP=-0.191 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ALAS2	NM_000032.5	c.1563C>G	p.Ser521Ser	synonymous_variant	Exon 10 of 11	ENST00000650242.1	NP_000023.2
ALAS2	NM_001037968.4	c.1524C>G	p.Ser508Ser	synonymous_variant	Exon 10 of 11		NP_001033057.1
ALAS2	NM_001037967.4	c.1452C>G	p.Ser484Ser	synonymous_variant	Exon 9 of 10		NP_001033056.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ALAS2	ENST00000650242.1	c.1563C>G	p.Ser521Ser	synonymous_variant	Exon 10 of 11		NM_000032.5	ENSP00000497236.1
ALAS2	ENST00000396198.7	c.1524C>G	p.Ser508Ser	synonymous_variant	Exon 10 of 11	5		ENSP00000379501.3
ALAS2	ENST00000335854.8	c.1452C>G	p.Ser484Ser	synonymous_variant	Exon 9 of 10	2		ENSP00000337131.4
ALAS2	ENST00000498636.1	c.726+1224C>G		intron_variant	Intron 4 of 4	3		ENSP00000495662.1

Frequencies

GnomAD3 genomes Cov.: 23

GnomAD4 exome AF: 0.00000455 AC: 5 AN: 1097899 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 363263

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.000123

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 23

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.58
CADD	Benign	6.4
DANN	Benign	0.71
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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-55039956;