4-144116864-C-T

Variant names:

• chr4-144116864-C-T
• rs772099477
• NM_002099.8:c.347G>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_002099.8(GYPA):​c.347G>A​(p.Arg116Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000424 in 1,580,600 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/20 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. R116L) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.000026 (0 hom., cov: 33)
  • Exomes 𝑓: 0.000044 (0 hom.)
• Consequence: GYPA NM_002099.8 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.07
• Publications: 1 publications found

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

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

• BP4: Computational evidence support a benign effect (MetaRNN=0.25053465).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002099.8. 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
	GYPA	NM_002099.8	MANE Select	c.347G>A	p.Arg116Gln	missense	Exon 5 of 7	NP_002090.4	P02724-1
	GYPA	NM_001438046.1		c.347G>A	p.Arg116Gln	missense	Exon 5 of 6	NP_001424975.1	A0A2R8Y7F9
	GYPA	NM_001308187.2		c.308G>A	p.Arg103Gln	missense	Exon 4 of 6	NP_001295116.1	E9PD10

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GYPA	ENST00000641688.3	MANE Select	c.347G>A	p.Arg116Gln	missense	Exon 5 of 7	ENSP00000493142.2	P02724-1
	GYPA	ENST00000360771.8	TSL:1	c.347G>A	p.Arg116Gln	missense	Exon 5 of 7	ENSP00000354003.4	P02724-1
	GYPA	ENST00000535709.6	TSL:1	c.341G>A	p.Arg114Gln	missense	Exon 6 of 8	ENSP00000445398.2	A0A087WU29

Frequencies

GnomAD3 genomes AF: 0.0000263 AC: 4 AN: 152052 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000441

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000438 AC: 11 AN: 250984 AF XY: 0.0000516

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000579

Gnomad ASJ exome AF: 0.0000994

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000176

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000441 AC: 63 AN: 1428548 Hom.: 0 Cov.: 27 AF XY: 0.0000519 AC XY: 37 AN XY: 713154

African (AFR) AF: 0.0000305 AC: 1 AN: 32836

American (AMR) AF: 0.0000448 AC: 2 AN: 44670

Ashkenazi Jewish (ASJ) AF: 0.0000386 AC: 1 AN: 25934

East Asian (EAS) AF: 0.0000253 AC: 1 AN: 39480

South Asian (SAS) AF: 0.000269 AC: 23 AN: 85612

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53396

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5692

European-Non Finnish (NFE) AF: 0.0000287 AC: 31 AN: 1081654

Other (OTH) AF: 0.0000675 AC: 4 AN: 59274

GnomAD4 genome AF: 0.0000263 AC: 4 AN: 152052 Hom.: 0 Cov.: 33 AF XY: 0.0000135 AC XY: 1 AN XY: 74266

African (AFR) AF: 0.00 AC: 0 AN: 41408

American (AMR) AF: 0.00 AC: 0 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5186

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4820

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10582

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000441 AC: 3 AN: 68012

Other (OTH) AF: 0.00 AC: 0 AN: 2084

Alfa AF: 0.0000868 Hom.: 0

Bravo AF: 0.0000264

ExAC AF: 0.0000494 AC: 6

EpiCase AF: 0.0000545

EpiControl AF: 0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.41	T
BayesDel_noAF	Benign	-0.55
CADD	Benign	0.094
DANN	Uncertain	1.0
DEOGEN2	Benign	0.033	T
Eigen	Benign	-0.67
Eigen_PC	Benign	-0.91
FATHMM_MKL	Benign	0.0097	N
LIST_S2	Benign	0.73	T
M_CAP	Benign	0.015	T
MetaRNN	Benign	0.25	T
MetaSVM	Benign	-1.0	T
PhyloP100		-2.1
PrimateAI	Benign	0.20	T
PROVEAN	Benign	-1.6	N
REVEL	Benign	0.081
Sift	Benign	0.14	T
Sift4G	Benign	0.067	T
Polyphen		0.91	P
Vest4		0.20
MVP		0.15
MPC		0.13
ClinPred		0.13	T
GERP RS		-3.2
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
gMVP		0.026
Mutation Taster		=87/13	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: rs772099477; hg19: chr4-145038017; COSMIC: COSV51625872; COSMIC: COSV51625872;