4-155789753-C-T

Variant names:

• chr4-155789753-C-T
• NM_000857.5:c.337C>T

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_000857.5(GUCY1B1):​c.337C>T​(p.Pro113Ser) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: GUCY1B1 NM_000857.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.85
• Publications: 0 publications found

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

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000857.5. 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
	GUCY1B1	NM_000857.5	MANE Select	c.337C>T	p.Pro113Ser	missense	Exon 5 of 14	NP_000848.1	Q02153-1
	GUCY1B1	NM_001291951.3		c.403C>T	p.Pro135Ser	missense	Exon 6 of 15	NP_001278880.1	E9PCN2
	GUCY1B1	NM_001291952.3		c.277C>T	p.Pro93Ser	missense	Exon 6 of 15	NP_001278881.1	Q02153-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GUCY1B1	ENST00000264424.13	TSL:1 MANE Select	c.337C>T	p.Pro113Ser	missense	Exon 5 of 14	ENSP00000264424.8	Q02153-1
	GUCY1B1	ENST00000507146.5	TSL:1	c.133C>T	p.Pro45Ser	missense	Exon 6 of 15	ENSP00000422313.1	D6RC99
	GUCY1B1	ENST00000503520.5	TSL:1	c.337C>T	p.Pro113Ser	missense	Exon 5 of 14	ENSP00000420842.1	Q02153-2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 28

GnomAD4 genome Cov.: 33

EpiCase AF: 0.0000546

EpiControl AF: 0.00

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.96
BayesDel_addAF	Benign	-0.017	T
BayesDel_noAF	Benign	-0.26
CADD	Pathogenic	27
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.061	T
Eigen	Pathogenic	0.86
Eigen_PC	Pathogenic	0.86
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.97	D
M_CAP	Benign	0.021	T
MetaRNN	Uncertain	0.59	D
MetaSVM	Benign	-0.49	T
MutationAssessor	Uncertain	2.4	M
PhyloP100		7.8
PrimateAI	Pathogenic	0.86	D
PROVEAN	Pathogenic	-6.2	D
REVEL	Uncertain	0.35
Sift	Benign	0.12	T
Sift4G	Benign	0.16	T
Polyphen		0.98	D
Vest4		0.75
MutPred		0.72		Loss of glycosylation at T132 (P = 0.0264)
MVP		0.84
MPC		2.3
ClinPred		1.0	D
GERP RS		6.0
Varity_R		0.62
gMVP		0.85
Mutation Taster		=13/87	disease causing

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.080		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

hg19: chr4-156710905;