4-143876799-C-T

Variant names:

• chr4-143876799-C-T
• NM_198682.3:c.193G>A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_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. 13/20 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: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: GYPE NM_198682.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.57

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]

ENSG00000251600 (HGNC:):

ACMG classification

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=0.102105975).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GYPE	NM_198682.3	c.193G>A	p.Val65Ile	missense_variant	Exon 3 of 4	ENST00000358615.9	NP_941391.2
GYPE	NM_002102.4	c.193G>A	p.Val65Ile	missense_variant	Exon 3 of 4		NP_002093.2
LOC105377459	XR_001741861.1	n.1463+10723C>T		intron_variant	Intron 9 of 9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GYPE	ENST00000358615.9	c.193G>A	p.Val65Ile	missense_variant	Exon 3 of 4	1	NM_198682.3	ENSP00000351430.4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1458660 Hom.: 0 Cov.: 28 AF XY: 0.00 AC XY: 0 AN XY: 725740

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: 0.00000180

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	0.14
BayesDel_addAF	Benign	-0.27	T
BayesDel_noAF	Benign	-0.63
CADD	Benign	3.6
DANN	Uncertain	0.98
DEOGEN2	Benign	0.024	T;T
Eigen	Benign	-0.76
Eigen_PC	Benign	-0.89
FATHMM_MKL	Benign	0.028	N
LIST_S2	Benign	0.30	.;T
M_CAP	Benign	0.0019	T
MetaRNN	Benign	0.10	T;T
MetaSVM	Benign	-0.95	T
PrimateAI	Benign	0.28	T
PROVEAN	Benign	-0.52	N;N
REVEL	Benign	0.039
Sift	Benign	0.043	D;D
Sift4G	Benign	0.13	T;T
Polyphen		0.33	B;B
Vest4		0.084
MutPred		0.37		Loss of sheet (P = 0.0181);Loss of sheet (P = 0.0181);
MVP		0.099
MPC		0.013
ClinPred		0.094	T
GERP RS		1.8
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.032
gMVP		0.14

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: chr4-144797952;