4-155696940-G-C

Variant names:

• chr4-155696940-G-C
• NM_001130682.3:c.73G>C

Variant summary

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

The NM_001130682.3(GUCY1A1):​c.73G>C​(p.Val25Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,148 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V25I) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: GUCY1A1 NM_001130682.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.77

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=0.25836247).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GUCY1A1	NM_001130682.3	c.73G>C	p.Val25Leu	missense_variant	Exon 3 of 10	ENST00000506455.6	NP_001124154.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GUCY1A1	ENST00000506455.6	c.73G>C	p.Val25Leu	missense_variant	Exon 3 of 10	1	NM_001130682.3	ENSP00000424361.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461148 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 726946

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

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: 0.0000166

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.077
BayesDel_addAF	Benign	-0.098	T
BayesDel_noAF	Benign	-0.38
CADD	Benign	15
DANN	Uncertain	0.98
DEOGEN2	Benign	0.052	T;T;T;.;T;T;T
Eigen	Benign	-0.47
Eigen_PC	Benign	-0.37
FATHMM_MKL	Benign	0.30	N
LIST_S2	Benign	0.69	.;T;.;T;.;.;T
M_CAP	Benign	0.037	D
MetaRNN	Benign	0.26	T;T;T;T;T;T;T
MetaSVM	Benign	-0.42	T
PrimateAI	Benign	0.40	T
PROVEAN	Benign	0.020	N;.;N;N;N;N;N
REVEL	Benign	0.23
Sift	Benign	0.39	T;.;T;T;T;T;T
Sift4G	Benign	0.91	T;T;T;T;T;T;T
Polyphen		0.0010	B;.;B;.;B;B;B
Vest4		0.028
MutPred		0.15		Gain of glycosylation at S29 (P = 0.0102);Gain of glycosylation at S29 (P = 0.0102);Gain of glycosylation at S29 (P = 0.0102);Gain of glycosylation at S29 (P = 0.0102);Gain of glycosylation at S29 (P = 0.0102);Gain of glycosylation at S29 (P = 0.0102);Gain of glycosylation at S29 (P = 0.0102);
MVP		0.82
MPC		0.073
ClinPred		0.90	D
GERP RS		5.9
Varity_R		0.080
gMVP		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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr4-156618092;