Variant 11-5232998-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP5_Moderate

The NM_000519.4(HBD):c.410G>A(p.Gly137Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000434 in 1,614,078 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Pathogenic (★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.00023 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000024 ( 0 hom. )

Consequence

HBD
NM_000519.4 missense

Scores

Clinical Significance

Pathogenic criteria provided, single submitter P:1O:1

Conservation

PhyloP100: 0.135

Variant links:

Genes affected

HBD (HGNC:4829): (hemoglobin subunit delta) The delta (HBD) and beta (HBB) genes are normally expressed in the adult: two alpha chains plus two beta chains constitute HbA, which in normal adult life comprises about 97% of the total hemoglobin. Two alpha chains plus two delta chains constitute HbA-2, which with HbF comprises the remaining 3% of adult hemoglobin. Five beta-like globin genes are found within a 45 kb cluster on chromosome 11 in the following order: 5'-epsilon--Ggamma--Agamma--delta--beta-3'. Mutations in the delta-globin gene are associated with beta-thalassemia. [provided by RefSeq, Jul 2008]

HBD links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP5

Variant 11-5232998-C-T is Pathogenic according to our data. Variant chr11-5232998-C-T is described in ClinVar as [Pathogenic]. Clinvar id is 15044.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HBD	NM_000519.4 linkuse as main transcript	c.410G>A	p.Gly137Asp	missense_variant	3/3	ENST00000650601.1	NP_000510.1	P02042A0N071

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
HBD	ENST00000650601.1 linkuse as main transcript	c.410G>A	p.Gly137Asp	missense_variant	3/3		NM_000519.4	ENSP00000497529.1	P02042
HBD	ENST00000643122.1 linkuse as main transcript	c.410G>A	p.Gly137Asp	missense_variant	4/4			ENSP00000494708.1	P02042
HBD	ENST00000417377.1 linkuse as main transcript	c.187G>A	p.Val63Met	missense_variant	2/2	3		ENSP00000414741.1	C9JRG0
HBD	ENST00000292901.7 linkuse as main transcript	c.316-200G>A		intron_variant		3		ENSP00000292901.3	E9PFT6

Frequencies

GnomAD3 genomes

AF:

0.000217

AC:

AN:

152170

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000627

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000262

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00144

GnomAD3 exomes

AF:

0.0000676

AC:

AN:

251350

Hom.:

AF XY:

0.0000442

AC XY:

AN XY:

135846

show subpopulations

Gnomad AFR exome

AF:

0.000861

Gnomad AMR exome

AF:

0.0000289

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000880

Gnomad OTH exome

AF:

0.000163

GnomAD4 exome

AF:

0.0000239

AC:

AN:

1461790

Hom.:

Cov.:

AF XY:

0.0000206

AC XY:

AN XY:

727204

show subpopulations

Gnomad4 AFR exome

AF:

0.000687

Gnomad4 AMR exome

AF:

0.0000895

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000270

Gnomad4 OTH exome

AF:

0.0000828

GnomAD4 genome

AF:

0.000230

AC:

AN:

152288

Hom.:

Cov.:

AF XY:

0.000242

AC XY:

AN XY:

74480

show subpopulations

Gnomad4 AFR

AF:

0.000674

Gnomad4 AMR

AF:

0.000262

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00142

Alfa

AF:

0.0000484

Hom.:

Bravo

AF:

0.000295

ESP6500AA

AF:

0.000909

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.0000906

AC:

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:1Other:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Pathogenic:1

Pathogenic, criteria provided, single submitter

clinical testing

Mayo Clinic Laboratories, Mayo Clinic

Jul 26, 2022

- -

HEMOGLOBIN A(2) BABINGA

Other:1

other, no assertion criteria provided

literature only

OMIM

Dec 12, 2017

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.90

BayesDel_addAF

Uncertain

0.15

BayesDel_noAF

Pathogenic

0.38

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.070

T;T;T

Eigen

Benign

0.094

Eigen_PC

Benign

0.018

FATHMM_MKL

Benign

0.26

LIST_S2

Benign

0.81

.;.;T

M_CAP

Pathogenic

0.56

MetaRNN

Uncertain

0.48

T;T;T

MetaSVM

Uncertain

0.29

MutationAssessor

Pathogenic

3.6

H;H;H

PrimateAI

Benign

0.43

PROVEAN

Uncertain

-2.9

.;D;.

REVEL

Pathogenic

0.80

Sift

Pathogenic

0.0

.;D;.

Sift4G

Benign

0.62

.;T;.

Polyphen

0.91

P;P;P

Vest4

0.76

MVP

0.98

MPC

0.069

ClinPred

0.40

GERP RS

3.9

Varity_R

0.67

gMVP

0.60

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over