4-144120546-A-G

Variant names:

• chr4-144120546-A-G
• NM_002099.8:c.80T>C

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BP4_Moderate BP6_Moderate

The NM_002099.8(GYPA):​c.80T>C​(p.Met27Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 13/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: not found (cov: 19)
  • Exomes 𝑓: 0.0000018 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: GYPA NM_002099.8 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.51

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 Likely_benign. Variant got -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.13084376).
• BP6: Variant 4-144120546-A-G is Benign according to our data. Variant chr4-144120546-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 3103372.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GYPA	NM_002099.8	c.80T>C	p.Met27Thr	missense_variant	Exon 2 of 7	ENST00000641688.3	NP_002090.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GYPA	ENST00000641688.3	c.80T>C	p.Met27Thr	missense_variant	Exon 2 of 7		NM_002099.8	ENSP00000493142.2

Frequencies

GnomAD3 genomes Cov.: 19

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00000179 AC: 2 AN: 1116236 Hom.: 0 Cov.: 31 AF XY: 0.00000358 AC XY: 2 AN XY: 558108

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.0000315

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: 0.00000119

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 19

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Nov 22, 2023

Ambry Genetics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Benign	-0.32	T
BayesDel_noAF	Benign	-0.69
CADD	Benign	0.0010
DANN	Benign	0.44
DEOGEN2	Benign	0.037	.;T;T;.;.;.;.;T;.;.
Eigen	Benign	-1.7
Eigen_PC	Benign	-1.9
FATHMM_MKL	Benign	0.0026	N
LIST_S2	Benign	0.63	T;.;T;T;.;.;D;T;T;T
M_CAP	Benign	0.0076	T
MetaRNN	Benign	0.076	T;T;T;T;T;T;T;T;T;T
MetaSVM	Benign	-0.87	T
PrimateAI	Benign	0.31	T
PROVEAN	Benign	-2.3	.;.;N;.;.;.;.;N;N;D
REVEL	Benign	0.062
Sift	Benign	0.26	.;.;T;.;.;.;.;T;T;T
Sift4G	Benign	0.20	T;.;T;.;.;T;.;T;T;T
Polyphen		0.26, 0.080	.;.;.;.;.;.;.;B;B;.
Vest4		0.061
MutPred		0.23		.;Gain of glycosylation at M27 (P = 0.0095);Gain of glycosylation at M27 (P = 0.0095);Gain of glycosylation at M27 (P = 0.0095);.;.;.;Gain of glycosylation at M27 (P = 0.0095);Gain of glycosylation at M27 (P = 0.0095);Gain of glycosylation at M27 (P = 0.0095);
MVP		0.030
MPC		0.039
ClinPred		0.53	D
GERP RS		-5.4
gMVP		0.031

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: chr4-145041699;