NM_000857.5:c.620G>T

Variant names:

• chr4-155793980-G-T
• rs369391839
• NM_000857.5:c.620G>T

Variant summary

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

The NM_000857.5(GUCY1B1):​c.620G>T​(p.Arg207Leu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000144 in 1,457,334 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.000014 (0 hom.)
• Consequence: GUCY1B1 NM_000857.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 9.60

Genes affected

GUCY1B1 (HGNC:4687): (guanylate cyclase 1 soluble subunit beta 1) This gene encodes the beta subunit of the soluble guanylate cyclase (sGC), which catalyzes the conversion of GTP (guanosine triphosphate) to cGMP (cyclic guanosine monophosphate). The encoded protein contains an HNOX domain, which serves as a receptor for ligands such as nitric oxide, oxygen and nitrovasodilator drugs. Alternative splicing results in multiple transcript variants. [provided by RefSeq, May 2014]

ACMG classification

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 rank	MANE	Protein	UniProt
GUCY1B1	NM_000857.5	c.620G>T	p.Arg207Leu	missense_variant	Exon 6 of 14	ENST00000264424.13	NP_000848.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GUCY1B1	ENST00000264424.13	c.620G>T	p.Arg207Leu	missense_variant	Exon 6 of 14	1	NM_000857.5	ENSP00000264424.8

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.0000144 AC: 21 AN: 1457334 Hom.: 0 Cov.: 29 AF XY: 0.0000124 AC XY: 9 AN XY: 725356

Gnomad4 AFR exome AF: 0.0000599

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: 0.0000171

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.41
BayesDel_addAF	Pathogenic	0.38	D
BayesDel_noAF	Pathogenic	0.30
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Benign	0.025	T;.;.;.;T;.;T
Eigen	Benign	0.033
Eigen_PC	Uncertain	0.29
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.97	.;D;D;D;D;D;D
M_CAP	Benign	0.058	D
MetaRNN	Uncertain	0.67	D;D;D;D;D;D;D
MetaSVM	Uncertain	-0.27	T
MutationAssessor	Benign	0.28	.;.;.;.;N;N;.
PrimateAI	Uncertain	0.77	T
PROVEAN	Benign	-1.8	N;N;N;N;N;N;N
REVEL	Uncertain	0.47
Sift	Benign	0.29	T;T;T;T;T;T;T
Sift4G	Benign	0.80	T;T;T;T;T;T;T
Polyphen		0.026, 0.064, 0.0050, 0.037	.;B;.;B;B;B;.
Vest4		0.94
MutPred		0.58		.;Gain of glycosylation at S231 (P = 0.0313);.;.;.;.;.;
MVP		0.87
MPC		0.012
ClinPred		0.66	D
GERP RS		5.9
Varity_R		0.78
gMVP		0.76

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.060		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: rs369391839; hg19: chr4-156715132;