rs753693249

Variant names:

• chr4-144120558-G-A
• rs753693249
• NM_002099.8:c.68C>T

Your query was ambiguous. Multiple possible variants found:

• chr4-144120558-G-A
• chr4-144120558-G-C
• chr4-144120558-G-T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_002099.8(GYPA):​c.68C>T​(p.Thr23Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 12/19 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. T23N) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 20)
  • Exomes 𝑓: 9.0e-7 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: GYPA NM_002099.8 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.722

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

Verdict is Likely_benign. Variant got -2 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.11548829).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GYPA	NM_002099.8	c.68C>T	p.Thr23Ile	missense_variant	Exon 2 of 7	ENST00000641688.3	NP_002090.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GYPA	ENST00000641688.3	c.68C>T	p.Thr23Ile	missense_variant	Exon 2 of 7		NM_002099.8	ENSP00000493142.2

Frequencies

GnomAD3 genomes Cov.: 20

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 8.97e-7 AC: 1 AN: 1114430 Hom.: 0 Cov.: 29 AF XY: 0.00 AC XY: 0 AN XY: 557996

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: 0.00

Gnomad4 NFE exome AF: 0.00000120

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 20

ExAC AF: 0.0000212 AC: 2

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.27
BayesDel_addAF	Benign	-0.17	T
BayesDel_noAF	Benign	-0.48
CADD	Benign	13
DANN	Uncertain	1.0
DEOGEN2	Benign	0.14	.;T;T;.;.;T;.;.
Eigen	Benign	-0.28
Eigen_PC	Benign	-0.55
FATHMM_MKL	Benign	0.085	N
LIST_S2	Uncertain	0.86	D;.;D;D;.;D;D;D
M_CAP	Benign	0.0033	T
MetaRNN	Benign	0.12	T;T;T;T;T;T;T;T
MetaSVM	Benign	-1.1	T
PrimateAI	Benign	0.28	T
PROVEAN	Uncertain	-3.5	.;.;D;.;N;D;D;D
REVEL	Benign	0.067
Sift	Uncertain	0.0010	.;.;D;.;T;D;D;D
Sift4G	Uncertain	0.0090	D;.;D;.;D;D;D;D
Polyphen		1.0, 0.97	.;.;.;.;.;D;D;.
Vest4		0.17
MutPred		0.32		.;Loss of glycosylation at T23 (P = 0.017);Loss of glycosylation at T23 (P = 0.017);Loss of glycosylation at T23 (P = 0.017);.;Loss of glycosylation at T23 (P = 0.017);Loss of glycosylation at T23 (P = 0.017);Loss of glycosylation at T23 (P = 0.017);
MVP		0.20
MPC		0.16
ClinPred		0.70	D
GERP RS		1.7
gMVP		0.047

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		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: rs753693249; hg19: chr4-145041711;