4-144120554-C-G

Variant names:

• chr4-144120554-C-G
• rs7658293
• NM_002099.8:c.72G>C

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_002099.8(GYPA):​c.72G>C​(p.Glu24Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 19)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: GYPA NM_002099.8 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.682
• Publications: 14 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: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.048533857).

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GYPA	NM_002099.8	MANE Select	c.72G>C	p.Glu24Asp	missense	Exon 2 of 7	NP_002090.4
	GYPA	NM_001438046.1		c.72G>C	p.Glu24Asp	missense	Exon 2 of 6	NP_001424975.1
	GYPA	NM_001308187.2		c.72G>C	p.Glu24Asp	missense	Exon 2 of 6	NP_001295116.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GYPA	ENST00000641688.3	MANE Select	c.72G>C	p.Glu24Asp	missense	Exon 2 of 7	ENSP00000493142.2
	GYPA	ENST00000360771.8	TSL:1	c.72G>C	p.Glu24Asp	missense	Exon 2 of 7	ENSP00000354003.4
	GYPA	ENST00000535709.6	TSL:1	c.66G>C	p.Glu22Asp	missense	Exon 3 of 8	ENSP00000445398.2

Frequencies

GnomAD3 genomes Cov.: 19

GnomAD2 exomes AF: 0.00 AC: 0 AN: 157362 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AC0;AS_VQSR AF: 0.00 AC: 0 AN: 1068260 Hom.: 0 Cov.: 29 AF XY: 0.00 AC XY: 0 AN XY: 535100

African (AFR) AF: 0.00 AC: 0 AN: 27038

American (AMR) AF: 0.00 AC: 0 AN: 31090

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 20414

East Asian (EAS) AF: 0.00 AC: 0 AN: 34020

South Asian (SAS) AF: 0.00 AC: 0 AN: 67698

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 42064

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3946

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 796456

Other (OTH) AF: 0.00 AC: 0 AN: 45534

GnomAD4 genome Cov.: 19

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Benign	-0.35	T
BayesDel_noAF	Benign	-0.74
CADD	Benign	0.79
DANN	Benign	0.41
DEOGEN2	Benign	0.023	T
Eigen	Benign	-1.4
Eigen_PC	Benign	-1.5
FATHMM_MKL	Benign	0.050	N
LIST_S2	Benign	0.54	T
M_CAP	Benign	0.0020	T
MetaRNN	Benign	0.049	T
MetaSVM	Benign	-0.95	T
PhyloP100		0.68
PrimateAI	Benign	0.23	T
PROVEAN	Benign	-0.83	N
REVEL	Benign	0.025
Sift	Benign	0.45	T
Sift4G	Benign	0.64	T
Polyphen		0.61	P
Vest4		0.053
MutPred		0.31		Loss of glycosylation at T23 (P = 0.0157)
MVP		0.095
MPC		0.040
ClinPred		0.17	T
GERP RS		-1.8
gMVP		0.018
Mutation Taster		=97/3	polymorphism

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

Other links and lift over

dbSNP: rs7658293; hg19: chr4-145041707;