11-106939519-A-C

Variant names:

• chr11-106939519-A-C
• NM_000855.3:c.1147T>G

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_000855.3(GUCY1A2):​c.1147T>G​(p.Ser383Ala) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. 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)
• Consequence: GUCY1A2 NM_000855.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.55

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]

ACMG classification

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=0.30253527).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GUCY1A2	NM_000855.3	c.1147T>G	p.Ser383Ala	missense_variant	Exon 4 of 8	ENST00000526355.7	NP_000846.1
GUCY1A2	NM_001256424.2	c.1147T>G	p.Ser383Ala	missense_variant	Exon 4 of 9		NP_001243353.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GUCY1A2	ENST00000526355.7	c.1147T>G	p.Ser383Ala	missense_variant	Exon 4 of 8	1	NM_000855.3	ENSP00000431245.2
GUCY1A2	ENST00000282249.6	c.1147T>G	p.Ser383Ala	missense_variant	Exon 4 of 9	1		ENSP00000282249.2
GUCY1A2	ENST00000347596.2	c.1147T>G	p.Ser383Ala	missense_variant	Exon 4 of 9	1		ENSP00000344874.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Mar 07, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.1147T>G (p.S383A) alteration is located in exon 4 (coding exon 4) of the GUCY1A2 gene. This alteration results from a T to G substitution at nucleotide position 1147, causing the serine (S) at amino acid position 383 to be replaced by an alanine (A). 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	0.080
BayesDel_addAF	Benign	-0.030	T
BayesDel_noAF	Benign	-0.28
CADD	Benign	21
DANN	Uncertain	0.99
DEOGEN2	Uncertain	0.69	D;.;.
Eigen	Benign	0.016
Eigen_PC	Benign	0.22
FATHMM_MKL	Uncertain	0.89	D
LIST_S2	Benign	0.65	T;T;T
M_CAP	Benign	0.034	D
MetaRNN	Benign	0.30	T;T;T
MetaSVM	Uncertain	-0.17	T
MutationAssessor	Benign	0.69	N;N;N
PrimateAI	Uncertain	0.60	T
PROVEAN	Uncertain	-2.6	D;D;D
REVEL	Uncertain	0.47
Sift	Benign	0.092	T;T;T
Sift4G	Benign	0.13	T;T;T
Polyphen		0.12	B;B;.
Vest4		0.21
MutPred		0.70		Loss of phosphorylation at S383 (P = 0.0501);Loss of phosphorylation at S383 (P = 0.0501);Loss of phosphorylation at S383 (P = 0.0501);
MVP		0.79
MPC		0.44
ClinPred		0.79	D
GERP RS		5.8
Varity_R		0.22
gMVP		0.22

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr11-106810245;