Variant 17-76537519-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_134268.5(CYGB):c.24G>A(p.Met8Ile) variant causes a missense change. The variant allele was found at a frequency of 0.00000191 in 1,571,716 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 (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

CYGB
NM_134268.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.77

Variant links:

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]

CYGB links:

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 links:

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ACMG classification

Classification made for transcript

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=0.30486897).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
CYGB	NM_134268.5 linkuse as main transcript	c.24G>A	p.Met8Ile	missense_variant	1/4	ENST00000293230.10	NP_599030.1
CYGB	XM_005257005.4 linkuse as main transcript	c.24G>A	p.Met8Ile	missense_variant	1/4		XP_005257062.1
CYGB	XM_017024116.2 linkuse as main transcript	c.-52-5828G>A		intron_variant			XP_016879605.1
PRCD	NR_033357.2 linkuse as main transcript	n.249-2986C>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CYGB	ENST00000293230.10 linkuse as main transcript	c.24G>A	p.Met8Ile	missense_variant	1/4	1	NM_134268.5	ENSP00000293230	P1

Frequencies

GnomAD3 genomes

AF:

0.00000659

AC:

AN:

151804

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000192

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

GnomAD4 exome

AF:

0.00000141

AC:

AN:

1419912

Hom.:

Cov.:

AF XY:

0.00000283

AC XY:

AN XY:

706558

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000292

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

9.14e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.00000659

AC:

AN:

151804

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74148

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000192

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Feb 13, 2024

The c.24G>A (p.M8I) alteration is located in exon 1 (coding exon 1) of the CYGB gene. This alteration results from a G to A substitution at nucleotide position 24, causing the methionine (M) at amino acid position 8 to be replaced by an isoleucine (I). 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

0.33

BayesDel_addAF

Uncertain

0.085

BayesDel_noAF

Benign

-0.12

CADD

Benign

DANN

Uncertain

0.98

DEOGEN2

Benign

0.29

T;.

Eigen

Benign

-0.29

Eigen_PC

Benign

-0.13

FATHMM_MKL

Benign

0.75

LIST_S2

Benign

0.79

T;T

M_CAP

Pathogenic

0.92

MetaRNN

Benign

0.30

T;T

MetaSVM

Uncertain

-0.17

MutationAssessor

Benign

1.1

L;.

MutationTaster

Benign

0.66

D;D;D

PrimateAI

Pathogenic

0.88

PROVEAN

Benign

-0.77

N;.

REVEL

Benign

0.26

Sift

Benign

0.46

T;.

Sift4G

Benign

0.46

T;T

Polyphen

0.0

B;.

Vest4

0.41

MutPred

0.22

Loss of catalytic residue at V4 (P = 0.012);Loss of catalytic residue at V4 (P = 0.012);

MVP

0.91

MPC

0.63

ClinPred

0.59

GERP RS

3.9

Varity_R

0.41

gMVP

0.69

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over