4-143876799-C-A

Variant names:

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

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_198682.3(GYPE):​c.193G>T​(p.Val65Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000206 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: 0.0000021 (0 hom.)
• Consequence: GYPE NM_198682.3 missense
• Clinical Significance: Not reported in ClinVar
• 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: 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=0.16269943).

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>T	p.Val65Phe	missense	Exon 3 of 4	NP_941391.2	P15421
	GYPE	NM_002102.4		c.193G>T	p.Val65Phe	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>T	p.Val65Phe	missense	Exon 3 of 4	ENSP00000351430.4	P15421
	GYPE	ENST00000437468.2	TSL:1	c.193G>T	p.Val65Phe	missense	Exon 3 of 4	ENSP00000400698.2	P15421
	GYPE	ENST00000506264.5	TSL:5	n.137-3324G>T		intron	N/A	ENSP00000426746.1	E9PCN6

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00000808 AC: 2 AN: 247392 AF XY: 0.0000149

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000583

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000206 AC: 3 AN: 1458660 Hom.: 0 Cov.: 28 AF XY: 0.00000413 AC XY: 3 AN XY: 725740

African (AFR) AF: 0.00 AC: 0 AN: 33402

American (AMR) AF: 0.0000448 AC: 2 AN: 44602

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 39574

South Asian (SAS) AF: 0.00 AC: 0 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: 9.01e-7 AC: 1 AN: 1109638

Other (OTH) AF: 0.00 AC: 0 AN: 60266

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.15
BayesDel_addAF	Benign	-0.31	T
BayesDel_noAF	Benign	-0.51
CADD	Benign	9.9
DANN	Uncertain	0.98
DEOGEN2	Benign	0.037	T
Eigen	Benign	-0.60
Eigen_PC	Benign	-0.78
FATHMM_MKL	Benign	0.041	N
LIST_S2	Benign	0.32	T
M_CAP	Benign	0.0030	T
MetaRNN	Benign	0.16	T
MetaSVM	Benign	-0.92	T
PhyloP100		1.6
PrimateAI	Benign	0.28	T
PROVEAN	Benign	-1.2	N
REVEL	Benign	0.080
Sift	Uncertain	0.029	D
Sift4G	Uncertain	0.059	T
Polyphen		0.80	P
Vest4		0.23
MutPred		0.49		Loss of sheet (P = 0.003)
MVP		0.24
MPC		0.012
ClinPred		0.087	T
GERP RS		1.8
Varity_R		0.072
gMVP		0.41
Mutation Taster		=94/6	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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;