chr11-106978739-A-G
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_000855.3(GUCY1A2):c.367T>C(p.Tyr123His) variant causes a missense, splice region change. The variant allele was found at a frequency of 0.0000214 in 1,590,150 control chromosomes in the GnomAD database, with no homozygous occurrence. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.000020 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000022 ( 0 hom. )
Consequence
GUCY1A2
NM_000855.3 missense, splice_region
NM_000855.3 missense, splice_region
Scores
10
9
Splicing: ADA: 0.3885
2
Clinical Significance
Conservation
PhyloP100: 6.35
Genes affected
GUCY1A2 (HGNC:4684): (guanylate cyclase 1 soluble subunit alpha 2) Soluble guanylate cyclases are heterodimeric proteins that catalyze the conversion of GTP to 3',5'-cyclic GMP and pyrophosphate. The protein encoded by this gene is an alpha subunit of this complex and it interacts with a beta subunit to form the guanylate cyclase enzyme, which is activated by nitric oxide. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jan 2012]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 2 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
GUCY1A2 | NM_000855.3 | c.367T>C | p.Tyr123His | missense_variant, splice_region_variant | 3/8 | ENST00000526355.7 | |
GUCY1A2 | NM_001256424.2 | c.367T>C | p.Tyr123His | missense_variant, splice_region_variant | 3/9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
GUCY1A2 | ENST00000526355.7 | c.367T>C | p.Tyr123His | missense_variant, splice_region_variant | 3/8 | 1 | NM_000855.3 | P1 | |
GUCY1A2 | ENST00000282249.6 | c.367T>C | p.Tyr123His | missense_variant, splice_region_variant | 3/9 | 1 | |||
GUCY1A2 | ENST00000347596.2 | c.367T>C | p.Tyr123His | missense_variant, splice_region_variant | 3/9 | 1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000197 AC: 3AN: 152230Hom.: 0 Cov.: 32
GnomAD3 genomes
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GnomAD3 exomes AF: 0.00000870 AC: 2AN: 229974Hom.: 0 AF XY: 0.0000161 AC XY: 2AN XY: 124274
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GnomAD4 exome AF: 0.0000216 AC: 31AN: 1437920Hom.: 0 Cov.: 27 AF XY: 0.0000252 AC XY: 18AN XY: 715332
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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 | Mar 27, 2023 | The c.367T>C (p.Y123H) alteration is located in exon 3 (coding exon 3) of the GUCY1A2 gene. This alteration results from a T to C substitution at nucleotide position 367, causing the tyrosine (Y) at amino acid position 123 to be replaced by a histidine (H). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Uncertain
D
BayesDel_noAF
Uncertain
Cadd
Uncertain
Dann
Uncertain
DEOGEN2
Benign
T;.;.
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
D
LIST_S2
Benign
T;T;T
M_CAP
Benign
D
MetaRNN
Uncertain
D;D;D
MetaSVM
Uncertain
D
MutationAssessor
Benign
L;L;L
MutationTaster
Benign
D;D;D
PrimateAI
Uncertain
T
PROVEAN
Benign
N;N;N
REVEL
Uncertain
Sift
Benign
T;T;T
Sift4G
Benign
T;T;T
Polyphen
D;D;.
Vest4
MutPred
Gain of disorder (P = 0.0304);Gain of disorder (P = 0.0304);Gain of disorder (P = 0.0304);
MVP
MPC
0.68
ClinPred
D
GERP RS
Varity_R
gMVP
Splicing
Name
Calibrated prediction
Score
Prediction
dbscSNV1_ADA
Benign
dbscSNV1_RF
Benign
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at