rs386352315

Variant names:

• chr4-155696936-T-A
• rs386352315
• ENST00000393832.7:c.-706T>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001130685.3(GUCY1A1):​c.-637T>A variant causes a splice region change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (no stars).

• Frequency: Genomes: not found (cov: 33)
• Consequence: GUCY1A1 NM_001130685.3 splice_region
• Clinical Significance: Uncertain significance no assertion criteria provided U:1
• Conservation: PhyloP100: -0.245
• Publications: 0 publications found

Genes affected

GUCY1A1 (HGNC:4685): (guanylate cyclase 1 soluble subunit alpha 1) 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. Several transcript variants encoding a few different isoforms have been found for this gene. [provided by RefSeq, Jan 2012]

GUCY1A1 Gene-Disease associations (from GenCC):

• Moyamoya disease with early-onset achalasia

  Inheritance: AR Classification: STRONG, SUPPORTIVE Submitted by: Orphanet, Genomics England PanelApp

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.78).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001130685.3. 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
	GUCY1A1	NM_001130682.3	MANE Select	c.69T>A	p.Gly23Gly	synonymous	Exon 3 of 10	NP_001124154.1	Q02108-1
	GUCY1A1	NM_001130685.3		c.-637T>A		splice_region	Exon 3 of 10	NP_001124157.1
	GUCY1A1	NM_001440518.1		c.-637T>A		splice_region	Exon 4 of 11	NP_001427447.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GUCY1A1	ENST00000393832.7	TSL:1	c.-706T>A		splice_region	Exon 3 of 10	ENSP00000377418.3	J3KPQ8
	GUCY1A1	ENST00000506455.6	TSL:1 MANE Select	c.69T>A	p.Gly23Gly	synonymous	Exon 3 of 10	ENSP00000424361.1	Q02108-1
	GUCY1A1	ENST00000296518.11	TSL:1	c.69T>A	p.Gly23Gly	synonymous	Exon 3 of 10	ENSP00000296518.7	Q02108-1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 33

ClinVar

ClinVar submissions as Germline

Significance: Uncertain significance

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
-	1	-	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	4.5
DANN	Benign	0.78
PhyloP100		-0.24

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

Other links and lift over

dbSNP: rs386352315; hg19: chr4-156618088;