chr17-76537499-C-T

Variant names:

• chr17-76537499-C-T
• rs1162789890
• NM_134268.5:c.44G>A

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_134268.5(CYGB):​c.44G>A​(p.Arg15Gln) variant causes a missense change. The variant allele was found at a frequency of 0.00000127 in 1,579,446 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R15G) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.0000066 (0 hom., cov: 32)
  • Exomes 𝑓: 7.0e-7 (0 hom.)
• Consequence: CYGB NM_134268.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.21
• Publications: 0 publications found

Genes affected

CYGB (HGNC:16505): (cytoglobin) This gene encodes a globin protein found in vertebrate cells. The encoded protein is described as a hexacoordinate hemoglobin which binds ligand differently from the pentacoordinate hemoglobins involved in oxygen transport, and may be involved in protection during oxidative stress. This gene is located on chromosome 17 in the same region as a retinal gene which is mutated in progressive rod-cone degeneration, but in the opposite orientation. [provided by RefSeq, Jan 2012]

PRCD (HGNC:32528): (photoreceptor disc component) This gene is predominantly expressed in the retina, and mutations in this gene are the cause of autosomal recessive retinal degeneration in both humans and dogs. Alternatively spliced transcript variants have been found for this gene. [provided by RefSeq, Mar 2010]

PRCD Gene-Disease associations (from GenCC):

• retinitis pigmentosa 36

  Inheritance: AR Classification: DEFINITIVE, STRONG, MODERATE Submitted by: Labcorp Genetics (formerly Invitae), G2P, Ambry Genetics
• retinitis pigmentosa

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.33559144).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_134268.5. 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
	CYGB	NM_134268.5	MANE Select	c.44G>A	p.Arg15Gln	missense	Exon 1 of 4	NP_599030.1	Q8WWM9
	PRCD	NR_033357.2		n.249-3006C>T		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CYGB	ENST00000293230.10	TSL:1 MANE Select	c.44G>A	p.Arg15Gln	missense	Exon 1 of 4	ENSP00000293230.4	Q8WWM9
	PRCD	ENST00000397633.7	TSL:1	n.46-3006C>T		intron	N/A
	CYGB	ENST00000589342.1	TSL:3	c.44G>A	p.Arg15Gln	missense	Exon 1 of 3	ENSP00000466448.1	K7EMC7

Frequencies

GnomAD3 genomes AF: 0.00000658 AC: 1 AN: 151988 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000655

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.00 AC: 0 AN: 217746 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

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: 7.01e-7 AC: 1 AN: 1427458 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 710264

African (AFR) AF: 0.00 AC: 0 AN: 29828

American (AMR) AF: 0.0000240 AC: 1 AN: 41712

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25064

East Asian (EAS) AF: 0.00 AC: 0 AN: 35030

South Asian (SAS) AF: 0.00 AC: 0 AN: 83256

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 51294

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5676

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1096776

Other (OTH) AF: 0.00 AC: 0 AN: 58822

GnomAD4 genome AF: 0.00000658 AC: 1 AN: 151988 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 74262

African (AFR) AF: 0.00 AC: 0 AN: 41426

American (AMR) AF: 0.0000655 AC: 1 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3466

East Asian (EAS) AF: 0.00 AC: 0 AN: 5192

South Asian (SAS) AF: 0.00 AC: 0 AN: 4838

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10512

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 314

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 67970

Other (OTH) AF: 0.00 AC: 0 AN: 2092

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000113

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.14
BayesDel_addAF	Uncertain	0.072	D
BayesDel_noAF	Benign	-0.13
CADD	Uncertain	25
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.25	T
Eigen	Benign	-0.081
Eigen_PC	Benign	0.051
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Uncertain	0.92	D
M_CAP	Pathogenic	0.94	D
MetaRNN	Benign	0.34	T
MetaSVM	Uncertain	0.26	D
MutationAssessor	Benign	1.5	L
PhyloP100		5.2
PrimateAI	Pathogenic	0.85	D
PROVEAN	Benign	-0.88	N
REVEL	Uncertain	0.31
Sift	Benign	0.11	T
Sift4G	Benign	0.11	T
Polyphen		0.059	B
Vest4		0.16
MutPred		0.16		Gain of loop (P = 0.069)
MVP		0.93
MPC		1.5
ClinPred		0.89	D
GERP RS		3.9
PromoterAI		0.015	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.2
Varity_R		0.49
gMVP		0.47

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: rs1162789890; hg19: chr17-74533581; COSMIC: COSV53150071; COSMIC: COSV53150071;