chr4-143876799-C-G

Variant names:

• chr4-143876799-C-G
• rs766244851
• NM_198682.3:c.193G>C

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_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. 15/21 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
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.57
• Publications: 1 publications found

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]

GUSBP5 (HGNC:):

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.08912867).

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>C	p.Val65Leu	missense	Exon 3 of 4	NP_941391.2	P15421
	GYPE	NM_002102.4		c.193G>C	p.Val65Leu	missense	Exon 3 of 4	NP_002093.2	P15421

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GYPE	ENST00000358615.9	TSL:1 MANE Select	c.193G>C	p.Val65Leu	missense	Exon 3 of 4	ENSP00000351430.4	P15421
	GYPE	ENST00000437468.2	TSL:1	c.193G>C	p.Val65Leu	missense	Exon 3 of 4	ENSP00000400698.2	P15421
	GYPE	ENST00000506264.5	TSL:5	n.137-3324G>C		intron	N/A	ENSP00000426746.1	E9PCN6

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.0000283 AC: 7 AN: 247392 AF XY: 0.0000373

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 FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.000167

GnomAD4 exome AF: 0.0000254 AC: 37 AN: 1458660 Hom.: 0 Cov.: 28 AF XY: 0.0000344 AC XY: 25 AN XY: 725740

African (AFR) AF: 0.0000599 AC: 2 AN: 33402

American (AMR) AF: 0.0000224 AC: 1 AN: 44602

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26092

East Asian (EAS) AF: 0.000632 AC: 25 AN: 39574

South Asian (SAS) AF: 0.0000349 AC: 3 AN: 85968

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53362

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5756

European-Non Finnish (NFE) AF: 0.00000360 AC: 4 AN: 1109638

Other (OTH) AF: 0.0000332 AC: 2 AN: 60266

GnomAD4 genome Cov.: 32

Alfa AF: 0.0000312 Hom.: 0

Bravo AF: 0.00000756

ExAC AF: 0.0000165 AC: 2

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.20
BayesDel_addAF	Benign	-0.43	T
BayesDel_noAF	Benign	-0.63
CADD	Benign	6.4
DANN	Benign	0.93
DEOGEN2	Benign	0.039	T
Eigen	Benign	-0.82
Eigen_PC	Benign	-0.93
FATHMM_MKL	Benign	0.043	N
LIST_S2	Benign	0.31	T
M_CAP	Benign	0.0020	T
MetaRNN	Benign	0.089	T
MetaSVM	Benign	-0.97	T
PhyloP100		1.6
PrimateAI	Benign	0.28	T
PROVEAN	Benign	-1.1	N
REVEL	Benign	0.033
Sift	Benign	0.069	T
Sift4G	Benign	0.16	T
Polyphen		0.14	B
Vest4		0.11
MutPred		0.46		Loss of sheet (P = 0.003)
MVP		0.076
MPC		0.012
ClinPred		0.020	T
GERP RS		1.8
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.061
gMVP		0.24
Mutation Taster		=96/4	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: rs766244851; hg19: chr4-144797952;