Genetic Variant GUCA2A:p.Ala16Thr (chr1-42164667-C-T) – ACMG Classification: Likely_benign (-1 pts)

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 0P and 1B. BP4

The NM_033553.3(GUCA2A):c.46G>A(p.Ala16Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000232 in 1,550,806 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000033 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000022 ( 0 hom. )

Consequence

GUCA2A
NM_033553.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.341

Publications

0 publications found

Variant links:

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]

GUCA2A links:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -1 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.30039304).

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.46G>A	p.Ala16Thr	missense	Exon 1 of 3	NP_291031.2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
GUCA2A	ENST00000357001.3	TSL:1 MANE Select	c.46G>A	p.Ala16Thr	missense	Exon 1 of 3	ENSP00000349493.2	Q02747
GUCA2A	ENST00000888051.1		c.46G>A	p.Ala16Thr	missense	Exon 1 of 3	ENSP00000558110.1
GUCA2A	ENST00000949218.1		c.46G>A	p.Ala16Thr	missense	Exon 1 of 3	ENSP00000619277.1

Frequencies

GnomAD3 genomes

AF:

0.0000328

AC:

AN:

152236

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000482

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000196

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.000159

AC:

AN:

156902

AF XY:

0.0000968

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00101

Gnomad ASJ exome

AF:

0.00

Gnomad EAS 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:

0.0000222

AC:

AN:

1398570

Hom.:

Cov.:

AF XY:

0.0000130

AC XY:

AN XY:

689980

show subpopulations

African (AFR)

AF:

0.0000632

AC:

AN:

31622

American (AMR)

AF:

0.000755

AC:

AN:

35754

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25170

East Asian (EAS)

AF:

0.00

AC:

AN:

35824

South Asian (SAS)

AF:

0.00

AC:

AN:

79216

European-Finnish (FIN)

AF:

0.00

AC:

AN:

49322

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5202

European-Non Finnish (NFE)

AF:

9.27e-7

AC:

AN:

1078502

Other (OTH)

AF:

0.0000173

AC:

AN:

57958

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.456

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0000328

AC:

AN:

152236

Hom.:

Cov.:

AF XY:

0.0000538

AC XY:

AN XY:

74374

show subpopulations

African (AFR)

AF:

0.0000482

AC:

AN:

41464

American (AMR)

AF:

0.000196

AC:

AN:

15290

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5186

South Asian (SAS)

AF:

0.00

AC:

AN:

4832

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10632

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

68040

Other (OTH)

AF:

0.00

AC:

AN:

2094

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.485

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.0000529

ExAC

AF:

0.0000414

AC:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.43

BayesDel_noAF

Benign

-0.45

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.19

Eigen

Benign

0.016

Eigen_PC

Benign

-0.041

FATHMM_MKL

Benign

0.30

LIST_S2

Benign

0.69

M_CAP

Benign

0.015

MetaRNN

Benign

0.30

MetaSVM

Benign

-0.91

MutationAssessor

Uncertain

2.2

PhyloP100

0.34

PrimateAI

Benign

0.37

PROVEAN

Benign

-1.6

REVEL

Benign

0.17

Sift

Uncertain

0.015

Sift4G

Benign

0.26

Polyphen

0.96

Vest4

0.17

MutPred

0.72

Loss of catalytic residue at A16 (P = 0.1488)

MVP

0.29

MPC

0.0020

ClinPred

0.096

GERP RS

4.6

PromoterAI

-0.037

Neutral

(source)

Varity_R

0.11

gMVP

0.41

Mutation Taster

=86/14

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over