11-5249442-C-A

Position:

• chr11-5249442-C-A

Variant summary

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

The NM_000559.3(HBG1):​c.241G>T​(p.Asp81Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as other (no stars). Another nucleotide change resulting in the same amino acid substitution has been previously reported as Likely benign in UniProt. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. D81N) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 12)
  • Exomes 𝑓: 0.0000012 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: HBG1 NM_000559.3 missense
• Clinical Significance: other no assertion criteria provided O:1
• Conservation: PhyloP100: -0.946

Genes affected

HBG1 (HGNC:4831): (hemoglobin subunit gamma 1) The gamma globin genes (HBG1 and HBG2) are normally expressed in the fetal liver, spleen and bone marrow. Two gamma chains together with two alpha chains constitute fetal hemoglobin (HbF) which is normally replaced by adult hemoglobin (HbA) at birth. In some beta-thalassemias and related conditions, gamma chain production continues into adulthood. The two types of gamma chains differ at residue 136 where glycine is found in the G-gamma product (HBG2) and alanine is found in the A-gamma product (HBG1). The former is predominant at birth. The order of the genes in the beta-globin cluster is: 5'-epsilon -- gamma-G -- gamma-A -- delta -- beta--3'. [provided by RefSeq, Jul 2008]

ENSG00000284931 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HBG1	NM_000559.3	c.241G>T	p.Asp81Tyr	missense_variant	2/3	ENST00000330597.5	NP_000550.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HBG1	ENST00000330597.5	c.241G>T	p.Asp81Tyr	missense_variant	2/3	1	NM_000559.3	ENSP00000327431.4
ENSG00000284931	ENST00000642908.1	c.316-955G>T		intron_variant				ENSP00000495346.1

Frequencies

GnomAD3 genomes Cov.: 12

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00000124 AC: 1 AN: 807328 Hom.: 0 Cov.: 16 AF XY: 0.00 AC XY: 0 AN XY: 409882

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: 0.0000241

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 12

ClinVar

Significance: other

Submissions summary: Other:1

Revision: no assertion criteria provided

Submissions by phenotype

HEMOGLOBIN F (VICTORIA JUBILEE) Other:1

other, no assertion criteria provided

literature only

OMIM

Jul 15, 2011

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.42
BayesDel_addAF	Pathogenic	0.21	D
BayesDel_noAF	Uncertain	0.070
CADD	Benign	20
DANN	Uncertain	0.98
Eigen	Benign	-0.34
Eigen_PC	Benign	-0.69
FATHMM_MKL	Benign	0.19	N
LIST_S2	Benign	0.53	T
M_CAP	Benign	0.070	D
MetaRNN	Uncertain	0.65	D
MetaSVM	Uncertain	0.53	D
PrimateAI	Benign	0.42	T
PROVEAN	Pathogenic	-4.6	D
REVEL	Uncertain	0.63
Sift	Uncertain	0.0040	D
Sift4G	Pathogenic	0.0010	D
Polyphen		0.99	D
Vest4		0.40
MutPred		0.68		Loss of disorder (P = 0.014);
MVP		0.89
MPC		2.3
ClinPred		0.95	D
GERP RS		-2.6
gMVP		0.76

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

Other links and lift over

dbSNP: rs33947112; hg19: chr11-5270672;