Genetic Variant GYPE:p.Val65Ile (chr4-143876799-C-T) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_198682.3(GYPE):c.193G>A(p.Val65Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,458,660 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V65L) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

GYPE
NM_198682.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.57

Publications

0 publications found

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:

GUSBP5 (HGNC:):

GUSBP5 links:

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ACMG classification

Classification was made for transcript

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

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.102105975).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_198682.3. 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
	GYPE	NM_198682.3	MANE Select	c.193G>A	p.Val65Ile	missense	Exon 3 of 4	NP_941391.2	P15421
	GYPE	NM_002102.4		c.193G>A	p.Val65Ile	missense	Exon 3 of 4	NP_002093.2	P15421

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
GYPE	ENST00000358615.9	TSL:1 MANE Select	c.193G>A	p.Val65Ile	missense	Exon 3 of 4	ENSP00000351430.4	P15421
GYPE	ENST00000437468.2	TSL:1	c.193G>A	p.Val65Ile	missense	Exon 3 of 4	ENSP00000400698.2	P15421
GYPE	ENST00000506264.5	TSL:5	n.137-3324G>A		intron	N/A	ENSP00000426746.1	E9PCN6

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000137

AC:

AN:

1458660

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

725740

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33402

American (AMR)

AF:

0.00

AC:

AN:

44602

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26092

East Asian (EAS)

AF:

0.00

AC:

AN:

39574

South Asian (SAS)

AF:

0.00

AC:

AN:

85968

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53362

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5756

European-Non Finnish (NFE)

AF:

0.00000180

AC:

AN:

1109638

Other (OTH)

AF:

0.00

AC:

AN:

60266

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.575

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.14

BayesDel_addAF

Benign

-0.27

BayesDel_noAF

Benign

-0.63

CADD

Benign

3.6

(source)

DANN

Uncertain

0.98

DEOGEN2

Benign

0.024

Eigen

Benign

-0.76

Eigen_PC

Benign

-0.89

FATHMM_MKL

Benign

0.028

LIST_S2

Benign

0.30

M_CAP

Benign

0.0019

MetaRNN

Benign

0.10

MetaSVM

Benign

-0.95

PhyloP100

1.6

PrimateAI

Benign

0.28

PROVEAN

Benign

-0.52

REVEL

Benign

0.039

Sift

Benign

0.043

Sift4G

Benign

0.13

Polyphen

0.33

Vest4

0.084

MutPred

0.37

Loss of sheet (P = 0.0181)

MVP

0.099

MPC

0.013

ClinPred

0.094

GERP RS

1.8

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.032

gMVP

0.14

Mutation Taster

=96/4

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over