NM_002101.5:c.176T>A

Variant names:

• chr2-126693933-T-A
• NM_002101.5:c.176T>A

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_002101.5(GYPC):​c.176T>A​(p.Ile59Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000687 in 1,456,060 control chromosomes in the GnomAD database, with no homozygous occurrence. 12/21 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: 32)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: GYPC NM_002101.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.46

Genes affected

GYPC (HGNC:4704): (glycophorin C (Gerbich blood group)) Glycophorin C (GYPC) is an integral membrane glycoprotein. It is a minor species carried by human erythrocytes, but plays an important role in regulating the mechanical stability of red cells. A number of glycophorin C mutations have been described. The Gerbich and Yus phenotypes are due to deletion of exon 3 and 2, respectively. The Webb and Duch antigens, also known as glycophorin D, result from single point mutations of the glycophorin C gene. The glycophorin C protein has very little homology with glycophorins A and B. Alternate splicing results in multiple transcript variants. [provided by RefSeq, Feb 2012]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GYPC	NM_002101.5	c.176T>A	p.Ile59Asn	missense_variant	Exon 3 of 4	ENST00000259254.9	NP_002092.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GYPC	ENST00000259254.9	c.176T>A	p.Ile59Asn	missense_variant	Exon 3 of 4	1	NM_002101.5	ENSP00000259254.4
GYPC	ENST00000409836.3	c.119T>A	p.Ile40Asn	missense_variant	Exon 2 of 3	1		ENSP00000386904.3
GYPC	ENST00000356887.12	c.113T>A	p.Ile38Asn	missense_variant	Exon 4 of 5	1		ENSP00000349354.7

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.87e-7 AC: 1 AN: 1456060 Hom.: 0 Cov.: 29 AF XY: 0.00 AC XY: 0 AN XY: 724788

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000252

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.33
BayesDel_addAF	Benign	-0.076	T
BayesDel_noAF	Benign	-0.35
CADD	Benign	17
DANN	Benign	0.94
DEOGEN2	Benign	0.015	T;.;.
Eigen	Benign	0.13
Eigen_PC	Benign	0.036
FATHMM_MKL	Uncertain	0.85	D
LIST_S2	Benign	0.49	T;T;T
M_CAP	Benign	0.0075	T
MetaRNN	Uncertain	0.68	D;D;D
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.6	L;.;.
PrimateAI	Uncertain	0.50	T
PROVEAN	Uncertain	-2.9	D;D;D
REVEL	Benign	0.14
Sift	Benign	0.34	T;T;T
Sift4G	Benign	0.26	T;T;T
Polyphen		1.0	D;.;D
Vest4		0.72
MutPred		0.40		Gain of catalytic residue at I59 (P = 0.0107);.;.;
MVP		0.52
MPC		0.0096
ClinPred		0.93	D
GERP RS		4.0
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.13
gMVP		0.36

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr2-127451509;