Genetic Variant GYPE:p.Val65Leu (chr4-143876799-C-G) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_198682.3(GYPE):c.193G>C(p.Val65Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000254 in 1,458,660 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.000025 ( 0 hom. )

Consequence

GYPE
NM_198682.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.57

Variant links:

Genes affected

GYPE (HGNC:4705): (glycophorin E (MNS blood group)) The protein encoded by this gene is a sialoglycoprotein and a type I membrane protein. It is a member of a gene family with GPA and GPB genes. This encoded protein might carry the M blood group antigen. GYPA, GYPB, and GYPE are organized in tandem on chromosome 4. This gene might have derived from an ancestral gene common to the GPB gene by gene duplication. Two alternatively spliced transcript variants encoding the same protein have been described for this gene. [provided by RefSeq, Jul 2008]

GYPE links:

ENSG00000251600 (HGNC:):

ENSG00000251600 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.08912867).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GYPE	NM_198682.3 link	c.193G>C	p.Val65Leu	missense_variant	Exon 3 of 4	ENST00000358615.9	NP_941391.2	P15421
GYPE	NM_002102.4 link	c.193G>C	p.Val65Leu	missense_variant	Exon 3 of 4		NP_002093.2	P15421
LOC105377459	XR_001741861.1 link	n.1463+10723C>G		intron_variant	Intron 9 of 9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GYPE	ENST00000358615.9 link	c.193G>C	p.Val65Leu	missense_variant	Exon 3 of 4	1	NM_198682.3	ENSP00000351430.4		P15421

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000283

AC:

AN:

247392

Hom.:

AF XY:

0.0000373

AC XY:

AN XY:

134178

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000291

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000112

Gnomad SAS exome

AF:

0.0000990

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.000167

GnomAD4 exome

AF:

0.0000254

AC:

AN:

1458660

Hom.:

Cov.:

AF XY:

0.0000344

AC XY:

AN XY:

725740

show subpopulations

Gnomad4 AFR exome

AF:

0.0000599

Gnomad4 AMR exome

AF:

0.0000224

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000632

Gnomad4 SAS exome

AF:

0.0000349

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000360

Gnomad4 OTH exome

AF:

0.0000332

GnomAD4 genome

Cov.:

Alfa

AF:

0.0000312

Hom.:

Bravo

AF:

0.00000756

ExAC

AF:

0.0000165

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Apr 20, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.193G>C (p.V65L) alteration is located in exon 3 (coding exon 3) of the GYPE gene. This alteration results from a G to C substitution at nucleotide position 193, causing the valine (V) at amino acid position 65 to be replaced by a leucine (L). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.20

BayesDel_addAF

Benign

-0.43

BayesDel_noAF

Benign

-0.63

CADD

Benign

6.4

DANN

Benign

0.93

DEOGEN2

Benign

0.039

T;T

Eigen

Benign

-0.82

Eigen_PC

Benign

-0.93

FATHMM_MKL

Benign

0.043

LIST_S2

Benign

0.31

.;T

M_CAP

Benign

0.0020

MetaRNN

Benign

0.089

T;T

MetaSVM

Benign

-0.97

PrimateAI

Benign

0.28

PROVEAN

Benign

-1.1

N;N

REVEL

Benign

0.033

Sift

Benign

0.069

T;T

Sift4G

Benign

0.16

T;T

Polyphen

0.14

B;B

Vest4

0.11

MutPred

0.46

Loss of sheet (P = 0.003);Loss of sheet (P = 0.003);

MVP

0.076

MPC

0.012

ClinPred

0.020

GERP RS

1.8

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.061

gMVP

0.24

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over