4-144120567-A-T

Variant names:

• chr4-144120567-A-T
• rs7682260
• NM_002099.8:c.59T>A

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

The NM_002099.8(GYPA):​c.59T>A​(p.Leu20*) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. 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 0.0 (0 hom., cov: 19)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: GYPA NM_002099.8 stop_gained
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.112
• Publications: 25 publications found

Genes affected

GYPA (HGNC:4702): (glycophorin A (MNS blood group)) Glycophorins A (GYPA) and B (GYPB) are major sialoglycoproteins of the human erythrocyte membrane which bear the antigenic determinants for the MN and Ss blood groups. In addition to the M or N and S or s antigens that commonly occur in all populations, about 40 related variant phenotypes have been identified. These variants include all the variants of the Miltenberger complex and several isoforms of Sta, as well as Dantu, Sat, He, Mg, and deletion variants Ena, S-s-U- and Mk. Most of the variants are the result of gene recombinations between GYPA and GYPB. [provided by RefSeq, Jul 2008]

ENSG00000285783 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002099.8. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GYPA	NM_002099.8	MANE Select	c.59T>A	p.Leu20*	stop_gained	Exon 2 of 7	NP_002090.4	P02724-1
	GYPA	NM_001438046.1		c.59T>A	p.Leu20*	stop_gained	Exon 2 of 6	NP_001424975.1	A0A2R8Y7F9
	GYPA	NM_001308187.2		c.59T>A	p.Leu20*	stop_gained	Exon 2 of 6	NP_001295116.1	E9PD10

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GYPA	ENST00000641688.3	MANE Select	c.59T>A	p.Leu20*	stop_gained	Exon 2 of 7	ENSP00000493142.2	P02724-1
	GYPA	ENST00000360771.8	TSL:1	c.59T>A	p.Leu20*	stop_gained	Exon 2 of 7	ENSP00000354003.4	P02724-1
	GYPA	ENST00000535709.6	TSL:1	c.53T>A	p.Leu18*	stop_gained	Exon 3 of 8	ENSP00000445398.2	A0A087WU29

Frequencies

GnomAD3 genomes AF: 0.00 AC: 0 AN: 124256 Hom.: 0 Cov.: 19

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: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AC0;AS_VQSR AF: 0.00 AC: 0 AN: 1022682 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 514456

African (AFR) AF: 0.00 AC: 0 AN: 26480

American (AMR) AF: 0.00 AC: 0 AN: 32776

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 20046

East Asian (EAS) AF: 0.00 AC: 0 AN: 31740

South Asian (SAS) AF: 0.00 AC: 0 AN: 68762

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 39968

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3870

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 755630

Other (OTH) AF: 0.00 AC: 0 AN: 43410

GnomAD4 genome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 124256 Hom.: 0 Cov.: 19 AF XY: 0.00 AC XY: 0 AN XY: 59314

African (AFR) AF: 0.00 AC: 0 AN: 34016

American (AMR) AF: 0.00 AC: 0 AN: 11762

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3000

East Asian (EAS) AF: 0.00 AC: 0 AN: 4078

South Asian (SAS) AF: 0.00 AC: 0 AN: 3178

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 7660

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 270

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 57808

Other (OTH) AF: 0.00 AC: 0 AN: 1674

Alfa AF: 0.00 Hom.: 2331

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Benign	-0.10	T
BayesDel_noAF	Benign	-0.38
CADD	Pathogenic	26
DANN	Benign	0.94
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.5
FATHMM_MKL	Benign	0.020	N
PhyloP100		0.11
Vest4		0.48
GERP RS		-3.4
Mutation Taster		=109/91	disease causing (fs/PTC)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.060		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs7682260; hg19: chr4-145041720;