1-42164668-C-A

Variant names:

• chr1-42164668-C-A
• NM_033553.3:c.45G>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_033553.3(GUCA2A):​c.45G>T​(p.Trp15Cys) variant causes a missense 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. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: GUCA2A NM_033553.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.22
• Publications: 0 publications found

Genes affected

GUCA2A (HGNC:4682): (guanylate cyclase activator 2A) Predicted to enable guanylate cyclase activator activity. Predicted to be involved in positive regulation of guanylate cyclase activity and signal transduction. Predicted to be located in extracellular region. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.2191827).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_033553.3. 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
	GUCA2A	NM_033553.3	MANE Select	c.45G>T	p.Trp15Cys	missense	Exon 1 of 3	NP_291031.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GUCA2A	ENST00000357001.3	TSL:1 MANE Select	c.45G>T	p.Trp15Cys	missense	Exon 1 of 3	ENSP00000349493.2	Q02747
	GUCA2A	ENST00000888051.1		c.45G>T	p.Trp15Cys	missense	Exon 1 of 3	ENSP00000558110.1
	GUCA2A	ENST00000949218.1		c.45G>T	p.Trp15Cys	missense	Exon 1 of 3	ENSP00000619277.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1398956 Hom.: 0 Cov.: 29 AF XY: 0.00 AC XY: 0 AN XY: 690110

African (AFR) AF: 0.00 AC: 0 AN: 31628

American (AMR) AF: 0.00 AC: 0 AN: 35770

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25174

East Asian (EAS) AF: 0.00 AC: 0 AN: 35842

South Asian (SAS) AF: 0.00 AC: 0 AN: 79226

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 49326

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5242

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1078780

Other (OTH) AF: 0.00 AC: 0 AN: 57968

GnomAD4 genome Cov.: 33

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	Benign	0.20
BayesDel_addAF	Benign	-0.21	T
BayesDel_noAF	Benign	-0.54
CADD	Benign	17
DANN	Benign	0.78
DEOGEN2	Benign	0.22	T
Eigen	Benign	-0.61
Eigen_PC	Benign	-0.62
FATHMM_MKL	Benign	0.18	N
LIST_S2	Benign	0.63	T
M_CAP	Benign	0.012	T
MetaRNN	Benign	0.22	T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	1.8	L
PhyloP100		1.2
PrimateAI	Benign	0.41	T
PROVEAN	Benign	-1.9	N
REVEL	Benign	0.056
Sift	Benign	0.15	T
Sift4G	Benign	0.22	T
Polyphen		0.0050	B
Vest4		0.24
MutPred		0.69		Loss of helix (P = 0.2022)
MVP		0.17
MPC		0.0014
ClinPred		0.088	T
GERP RS		1.4
PromoterAI		-0.026	Neutral
Varity_R		0.15
gMVP		0.39
Mutation Taster		=96/4	polymorphism

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

hg19: chr1-42630339;