rs199885693
Variant names:
Your query was ambiguous. Multiple possible variants found:
Variant summary
Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate
The NM_001384910.1(GUCA1A):c.85T>A(p.Cys29Ser) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,560 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.
Frequency
Genomes: not found (cov: 33)
Exomes 𝑓: 6.8e-7 ( 0 hom. )
Consequence
GUCA1A
NM_001384910.1 missense
NM_001384910.1 missense
Scores
7
5
7
Clinical Significance
Not reported in ClinVar
Conservation
PhyloP100: 8.02
Genes affected
GUCA1A (HGNC:4678): (guanylate cyclase activator 1A) This gene encodes an enzyme that plays a role in the recovery of retinal photoreceptors from photobleaching. This enzyme promotes the activity of retinal guanylyl cyclase-1 (GC1) at low calcium concentrations and inhibits GC1 at high calcium concentrations. Mutations in this gene can cause cone dystrophy 3 and code-rod dystrophy 14. provided by RefSeq, Jul 2020]
ENSG00000290147 (HGNC:56129): (GUCA1ANB-GUCA1A readthrough) This locus represents naturally occurring readthrough transcription between the neighboring GUCA1ANB (GUCA1A neighbor) and GUCA1A (guanylate cyclase activator 1A) genes on chromosome 6. The readthrough transcript encodes the same protein as GUCA1A. [provided by RefSeq, Jul 2020]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 4 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.89
Transcripts
RefSeq
| Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|
| GUCA1A | NM_001384910.1 | c.85T>A | p.Cys29Ser | missense_variant | Exon 1 of 4 | ENST00000372958.2 | NP_001371839.1 | |
| GUCA1ANB-GUCA1A | NM_000409.5 | c.85T>A | p.Cys29Ser | missense_variant | Exon 3 of 6 | NP_000400.2 | ||
| GUCA1ANB-GUCA1A | NM_001319061.2 | c.85T>A | p.Cys29Ser | missense_variant | Exon 3 of 6 | NP_001305990.1 | ||
| GUCA1ANB-GUCA1A | NM_001319062.2 | c.85T>A | p.Cys29Ser | missense_variant | Exon 2 of 5 | NP_001305991.1 |
Ensembl
Frequencies
GnomAD3 genomes
GnomAD3 genomes
Cov.:
33
GnomAD4 exome AF: 6.84e-7 AC: 1AN: 1461560Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1AN XY: 727102
GnomAD4 exome
AF:
AC:
1
AN:
1461560
Hom.:
Cov.:
31
AF XY:
AC XY:
1
AN XY:
727102
Gnomad4 AFR exome
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GnomAD4 genome
GnomAD4 genome
Cov.:
33
ExAC
AF:
AC:
1
ClinVar
Not reported inComputational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Uncertain
DANN
Benign
DEOGEN2
Uncertain
.;.;D;D;D
Eigen
Pathogenic
Eigen_PC
Pathogenic
FATHMM_MKL
Pathogenic
D
LIST_S2
Benign
.;T;.;.;T
M_CAP
Benign
D
MetaRNN
Pathogenic
D;D;D;D;D
MetaSVM
Uncertain
T
MutationAssessor
Uncertain
.;.;M;M;M
PrimateAI
Pathogenic
D
PROVEAN
Pathogenic
D;.;D;D;D
REVEL
Uncertain
Sift
Benign
T;.;T;T;T
Sift4G
Uncertain
D;T;T;T;T
Polyphen
1.0
.;.;D;D;D
Vest4
0.52, 0.53, 0.52, 0.51
MutPred
Gain of disorder (P = 0.0046);.;Gain of disorder (P = 0.0046);Gain of disorder (P = 0.0046);Gain of disorder (P = 0.0046);
MVP
MPC
0.97
ClinPred
D
GERP RS
Varity_R
gMVP
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at