Genetic Variant GUCY2F:p.Ser962Ile (chrX-109388560-C-A) – ACMG Classification: Uncertain_significance (3 pts)

Variant summary

Our verdict is . The variant received 3 ACMG points: 3P and 0B. PM2PP3

The NM_001522.3(GUCY2F):c.2885G>T(p.Ser962Ile) variant causes a missense change. The variant allele was found at a frequency of 0.00000184 in 1,088,055 control chromosomes in the GnomAD database, with no homozygous occurrence. There are no hemizygote samples in GnomAD. In-silico tool predicts a pathogenic 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. S962N) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 23)

Exomes 𝑓: 0.0000018 ( 0 hom. 0 hem. )

Consequence

GUCY2F
NM_001522.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 5.98

Publications

1 publications found

Variant links:

Genes affected

GUCY2F (HGNC:4691): (guanylate cyclase 2F, retinal) The protein encoded by this gene is a guanylyl cyclase found predominantly in photoreceptors in the retina. The encoded protein is thought to be involved in resynthesis of cGMP after light activation of the visual signal transduction cascade, allowing a return to the dark state. This protein is a single-pass type I membrane protein. Defects in this gene may be a cause of X-linked retinitis pigmentosa. [provided by RefSeq, Dec 2008]

GUCY2F links:

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new If you want to explore the variant's impact on the transcript NM_001522.3, check out the Mutation Effect Viewer. This is especially useful for frameshift variants or if you want to visualize the effect of exon loss / intron retention.

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

REVEL computational evidence supports a deleterious effect, 0.733

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001522.3. 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
	GUCY2F	NM_001522.3	MANE Select	c.2885G>T	p.Ser962Ile	missense	Exon 15 of 20	NP_001513.2	P51841

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GUCY2F	ENST00000218006.3	TSL:1 MANE Select	c.2885G>T	p.Ser962Ile	missense	Exon 15 of 20	ENSP00000218006.2	P51841

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000547

AC:

AN:

182650

AF XY:

0.00

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000184

AC:

AN:

1088055

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

354183

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

26192

American (AMR)

AF:

0.00

AC:

AN:

35169

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

19311

East Asian (EAS)

AF:

0.00

AC:

AN:

30167

South Asian (SAS)

AF:

0.0000186

AC:

AN:

53854

European-Finnish (FIN)

AF:

0.00

AC:

AN:

40527

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3555

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

833583

Other (OTH)

AF:

0.0000219

AC:

AN:

45697

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.450

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.94

BayesDel_addAF

Uncertain

0.14

BayesDel_noAF

Uncertain

0.12

CADD

Uncertain

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.40

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Uncertain

0.96

M_CAP

Uncertain

0.11

MetaRNN

Pathogenic

0.84

MetaSVM

Uncertain

0.17

MutationAssessor

Uncertain

2.3

PhyloP100

6.0

PrimateAI

Uncertain

0.62

PROVEAN

Pathogenic

-4.7

REVEL

Pathogenic

0.73

Sift

Uncertain

0.023

Sift4G

Uncertain

0.016

Varity_R

0.86

gMVP

0.77

Mutation Taster

=43/57

disease causing

(source)

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over