chr4-144116930-A-T

Variant names:

• chr4-144116930-A-T
• NM_002099.8:c.281T>A

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM1 PM2

The NM_002099.8(GYPA):​c.281T>A​(p.Leu94His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000712 in 1,405,280 control chromosomes in the GnomAD database, with no homozygous occurrence. 11/19 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: 33)
  • Exomes 𝑓: 7.1e-7 (0 hom.)
• Consequence: GYPA NM_002099.8 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.842

Genes affected

GYPA (HGNC:4702): (glycophorin A (MNS blood group)) Glycophorins A (GYPA) and B (GYPB) are major sialoglycoproteins of the human erythrocyte membrane which bear the antigenic determinants for the MN and Ss blood groups. In addition to the M or N and S or s antigens that commonly occur in all populations, about 40 related variant phenotypes have been identified. These variants include all the variants of the Miltenberger complex and several isoforms of Sta, as well as Dantu, Sat, He, Mg, and deletion variants Ena, S-s-U- and Mk. Most of the variants are the result of gene recombinations between GYPA and GYPB. [provided by RefSeq, Jul 2008]

ENSG00000285783 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 4 ACMG points.

• PM1: In a mutagenesis_site Diminishes dimerization. (size 0) in uniprot entity GLPA_HUMAN
• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GYPA	NM_002099.8	c.281T>A	p.Leu94His	missense_variant	Exon 5 of 7	ENST00000641688.3	NP_002090.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GYPA	ENST00000641688.3	c.281T>A	p.Leu94His	missense_variant	Exon 5 of 7		NM_002099.8	ENSP00000493142.2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 7.12e-7 AC: 1 AN: 1405280 Hom.: 0 Cov.: 24 AF XY: 0.00 AC XY: 0 AN XY: 702998

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: 9.43e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.84
BayesDel_addAF	Benign	-0.16	T
BayesDel_noAF	Benign	-0.46
CADD	Benign	6.9
DANN	Benign	0.96
DEOGEN2	Benign	0.11	.;T;T;.;.;.;.;.;.;T;T;.;.;.
Eigen	Benign	-0.50
Eigen_PC	Benign	-0.80
FATHMM_MKL	Benign	0.030	N
LIST_S2	Benign	0.68	T;.;T;T;T;.;.;T;T;T;T;T;T;T
M_CAP	Benign	0.011	T
MetaRNN	Uncertain	0.61	D;D;D;D;D;D;D;D;D;D;D;D;D;D
MetaSVM	Benign	-0.95	T
PrimateAI	Benign	0.27	T
PROVEAN	Uncertain	-3.4	.;.;D;.;D;.;.;.;.;.;D;D;D;D
REVEL	Benign	0.094
Sift	Uncertain	0.011	.;.;D;.;D;.;.;.;.;.;D;D;D;D
Sift4G	Pathogenic	0.0010	D;.;D;.;D;.;D;.;.;.;D;D;D;D
Polyphen		1.0, 0.99	.;.;.;.;.;.;.;.;.;.;D;D;D;.
Vest4		0.52
MutPred		0.79		.;Gain of disorder (P = 0.0174);Gain of disorder (P = 0.0174);Gain of disorder (P = 0.0174);.;.;.;.;.;.;.;.;.;.;
MVP		0.16
MPC		0.17
ClinPred		0.76	D
GERP RS		-2.4
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
gMVP		0.028

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr4-145038083;