4-143876843-A-G

Variant names:

• chr4-143876843-A-G
• rs1269265873
• NM_198682.3:c.149T>C

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_198682.3(GYPE):​c.149T>C​(p.Ile50Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/20 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)
• Consequence: GYPE NM_198682.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.02

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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.35166723).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GYPE	NM_198682.3	c.149T>C	p.Ile50Thr	missense_variant	Exon 3 of 4	ENST00000358615.9	NP_941391.2
GYPE	NM_002102.4	c.149T>C	p.Ile50Thr	missense_variant	Exon 3 of 4		NP_002093.2
LOC105377459	XR_001741861.1	n.1463+10767A>G		intron_variant	Intron 9 of 9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GYPE	ENST00000358615.9	c.149T>C	p.Ile50Thr	missense_variant	Exon 3 of 4	1	NM_198682.3	ENSP00000351430.4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 27

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

May 08, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.149T>C (p.I50T) alteration is located in exon 3 (coding exon 3) of the GYPE gene. This alteration results from a T to C substitution at nucleotide position 149, causing the isoleucine (I) at amino acid position 50 to be replaced by a threonine (T). 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	0.19
BayesDel_addAF	Benign	-0.19	T
BayesDel_noAF	Benign	-0.51
CADD	Benign	16
DANN	Benign	0.97
DEOGEN2	Benign	0.034	T;T
Eigen	Benign	-0.54
Eigen_PC	Benign	-0.78
FATHMM_MKL	Benign	0.042	N
LIST_S2	Benign	0.22	.;T
M_CAP	Benign	0.0023	T
MetaRNN	Benign	0.35	T;T
MetaSVM	Benign	-0.99	T
PrimateAI	Uncertain	0.68	T
PROVEAN	Benign	-1.2	N;N
REVEL	Benign	0.082
Sift	Benign	0.26	T;T
Sift4G	Benign	0.064	T;T
Polyphen		0.99	D;D
Vest4		0.53
MutPred		0.40		Loss of helix (P = 0.0558);Loss of helix (P = 0.0558);
MVP		0.17
MPC		0.011
ClinPred		0.14	T
GERP RS		0.59
Varity_R		0.084
gMVP		0.055

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

Other links and lift over

dbSNP: rs1269265873; hg19: chr4-144797996;