Variant X-55009187-T-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_000032.5(ALAS2):c.1757A>C(p.Tyr586Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000009 in 111,073 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 1 hemizygotes 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: 𝑓 0.0000090 ( 0 hom., 1 hem., cov: 23)

Consequence

ALAS2
NM_000032.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.262

Variant links:

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]

ALAS2 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.11588526).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
ALAS2	NM_000032.5 linkuse as main transcript	c.1757A>C	p.Tyr586Ser	missense_variant	11/11	ENST00000650242.1	NP_000023.2
ALAS2	NM_001037968.4 linkuse as main transcript	c.1718A>C	p.Tyr573Ser	missense_variant	11/11		NP_001033057.1
ALAS2	NM_001037967.4 linkuse as main transcript	c.1646A>C	p.Tyr549Ser	missense_variant	10/10		NP_001033056.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ALAS2	ENST00000650242.1 linkuse as main transcript	c.1757A>C	p.Tyr586Ser	missense_variant	11/11		NM_000032.5	ENSP00000497236	P1	P22557-1
ALAS2	ENST00000396198.7 linkuse as main transcript	c.1718A>C	p.Tyr573Ser	missense_variant	11/11	5		ENSP00000379501		P22557-4
ALAS2	ENST00000335854.8 linkuse as main transcript	c.1646A>C	p.Tyr549Ser	missense_variant	10/10	2		ENSP00000337131		P22557-2
ALAS2	ENST00000498636.1 linkuse as main transcript	c.*55A>C		3_prime_UTR_variant	5/5	3		ENSP00000495662

Frequencies

GnomAD3 genomes

AF:

0.00000900

AC:

AN:

111073

Hom.:

Cov.:

AF XY:

0.0000300

AC XY:

AN XY:

33299

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000385

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

Cov.:

GnomAD4 genome

AF:

0.00000900

AC:

AN:

111073

Hom.:

Cov.:

AF XY:

0.0000300

AC XY:

AN XY:

33299

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000385

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.080

BayesDel_addAF

Uncertain

0.10

BayesDel_noAF

Benign

-0.090

CADD

Benign

DANN

Benign

0.86

DEOGEN2

Benign

0.20

.;T;T;.

FATHMM_MKL

Benign

0.40

LIST_S2

Benign

0.82

T;.;T;T

M_CAP

Pathogenic

0.30

MetaRNN

Benign

0.12

T;T;T;T

MetaSVM

Uncertain

0.27

MutationAssessor

Benign

0.26

.;N;N;.

MutationTaster

Benign

0.59

D;D;D

PrimateAI

Uncertain

0.59

PROVEAN

Benign

-0.51

N;.;N;N

REVEL

Uncertain

0.34

Sift

Benign

0.10

T;.;T;T

Sift4G

Benign

0.25

T;.;T;T

Polyphen

0.065

.;B;B;.

Vest4

0.21

MutPred

0.25

.;Gain of relative solvent accessibility (P = 0.005);Gain of relative solvent accessibility (P = 0.005);.;

MVP

0.78

MPC

0.71

ClinPred

0.052

GERP RS

4.2

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.16

gMVP

0.88

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over