ENST00000393832:c.-503T>A

Variant names:

• chr4-155703948-T-A
• rs753726676
• ENST00000393832:c.-503T>A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The ENST00000393832(GUCY1A1):​c.-503T>A variant causes a 5 prime UTR premature start codon gain change. The variant allele was found at a frequency of 0.00000137 in 1,454,574 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: GUCY1A1 ENST00000393832 5_prime_UTR_premature_start_codon_gain
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.28

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.17361602).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GUCY1A1	NM_001130682.3	c.272T>A	p.Val91Asp	missense_variant	Exon 4 of 10	ENST00000506455.6	NP_001124154.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GUCY1A1	ENST00000506455.6	c.272T>A	p.Val91Asp	missense_variant	Exon 4 of 10	1	NM_001130682.3	ENSP00000424361.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.00000807 AC: 2 AN: 247966 Hom.: 0 AF XY: 0.00000746 AC XY: 1 AN XY: 134058

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000601

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS 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: 0.00000137 AC: 2 AN: 1454574 Hom.: 0 Cov.: 28 AF XY: 0.00000138 AC XY: 1 AN XY: 723960

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.0000460

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000378

ExAC AF: 0.00000824 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.14
BayesDel_addAF	Benign	-0.30	T
BayesDel_noAF	Benign	-0.49
CADD	Benign	17
DANN	Benign	0.96
DEOGEN2	Benign	0.058	T;T;T;.;T;T;T
Eigen	Benign	-0.25
Eigen_PC	Benign	-0.0099
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Benign	0.47	.;T;.;T;.;.;T
M_CAP	Benign	0.0055	T
MetaRNN	Benign	0.17	T;T;T;T;T;T;T
MetaSVM	Benign	-1.1	T
PrimateAI	Benign	0.38	T
PROVEAN	Benign	-0.39	N;.;N;N;N;N;N
REVEL	Benign	0.059
Sift	Benign	0.64	T;.;T;T;T;T;T
Sift4G	Benign	0.61	T;D;T;T;T;T;T
Polyphen		0.0	B;.;B;.;B;B;B
Vest4		0.41
MutPred		0.41		Gain of disorder (P = 0.021);Gain of disorder (P = 0.021);Gain of disorder (P = 0.021);Gain of disorder (P = 0.021);Gain of disorder (P = 0.021);Gain of disorder (P = 0.021);Gain of disorder (P = 0.021);
MVP		0.51
MPC		0.12
ClinPred		0.27	T
GERP RS		5.6
Varity_R		0.38
gMVP		0.65

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

LitVar

Other links and lift over

dbSNP: rs753726676; hg19: chr4-156625100;