Variant 17-76537508-C-A 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.35G>T(p.Arg12Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000421 in 1,424,640 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: not found (cov: 32)

Exomes 𝑓: 0.0000042 ( 0 hom. )

Consequence

CYGB
NM_134268.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.12

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:):

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=0.41057453).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CYGB	NM_134268.5 linkuse as main transcript	c.35G>T	p.Arg12Leu	missense_variant	1/4	ENST00000293230.10	NP_599030.1	Q8WWM9A0A1K0FUB6
CYGB	XM_005257005.4 linkuse as main transcript	c.35G>T	p.Arg12Leu	missense_variant	1/4		XP_005257062.1
CYGB	XM_017024116.2 linkuse as main transcript	c.-52-5817G>T		intron_variant			XP_016879605.1
PRCD	NR_033357.2 linkuse as main transcript	n.249-2997C>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CYGB	ENST00000293230.10 linkuse as main transcript	c.35G>T	p.Arg12Leu	missense_variant	1/4	1	NM_134268.5	ENSP00000293230.4		Q8WWM9

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000928

AC:

AN:

215598

Hom.:

AF XY:

0.00000845

AC XY:

AN XY:

118292

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000749

Gnomad SAS exome

AF:

0.0000365

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000421

AC:

AN:

1424640

Hom.:

Cov.:

AF XY:

0.00000282

AC XY:

AN XY:

708862

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000576

Gnomad4 SAS exome

AF:

0.0000361

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.0000170

GnomAD4 genome

Cov.:

ExAC

AF:

0.0000165

AC:

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

Apr 26, 2023

The c.35G>T (p.R12L) alteration is located in exon 1 (coding exon 1) of the CYGB gene. This alteration results from a G to T substitution at nucleotide position 35, causing the arginine (R) at amino acid position 12 to be replaced by a leucine (L). 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

0.24

BayesDel_addAF

Uncertain

0.12

BayesDel_noAF

Uncertain

-0.070

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.37

T;.

Eigen

Benign

0.093

Eigen_PC

Benign

0.15

FATHMM_MKL

Uncertain

0.90

LIST_S2

Uncertain

0.89

D;D

M_CAP

Pathogenic

0.96

MetaRNN

Benign

0.41

T;T

MetaSVM

Uncertain

0.40

MutationAssessor

Benign

1.3

L;.

PrimateAI

Pathogenic

0.88

PROVEAN

Benign

-1.8

N;.

REVEL

Uncertain

0.52

Sift

Benign

0.14

T;.

Sift4G

Benign

0.26

T;T

Polyphen

0.80

P;.

Vest4

0.38

MutPred

0.25

Gain of sheet (P = 0.0477);Gain of sheet (P = 0.0477);

MVP

0.94

MPC

1.6

ClinPred

0.69

GERP RS

3.9

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.8

Varity_R

0.51

gMVP

0.51

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