6-42173622-C-T

Position:

chr6-42173622-C-T

Variant summary

Our verdict is Benign. Variant got -17 ACMG points: 0P and 17B. BP4_StrongBP6_Very_StrongBP7BS2

The NM_001384910.1(GUCA1A):c.9C>T(p.Asn3Asn) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000694 in 1,613,648 control chromosomes in the GnomAD database, including 7 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0036 ( 2 hom., cov: 33)

Exomes 𝑓: 0.00039 ( 5 hom. )

Consequence

GUCA1A
NM_001384910.1 synonymous

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 0.170

Variant links:

Genes affected

GUCA1A (HGNC:4678): (guanylate cyclase activator 1A) This gene encodes an enzyme that plays a role in the recovery of retinal photoreceptors from photobleaching. This enzyme promotes the activity of retinal guanylyl cyclase-1 (GC1) at low calcium concentrations and inhibits GC1 at high calcium concentrations. Mutations in this gene can cause cone dystrophy 3 and code-rod dystrophy 14. provided by RefSeq, Jul 2020]

GUCA1A links:

ENSG00000290147 (HGNC:56129): (GUCA1ANB-GUCA1A readthrough) This locus represents naturally occurring readthrough transcription between the neighboring GUCA1ANB (GUCA1A neighbor) and GUCA1A (guanylate cyclase activator 1A) genes on chromosome 6. The readthrough transcript encodes the same protein as GUCA1A. [provided by RefSeq, Jul 2020]

ENSG00000290147 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -17 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.53).

BP6

Variant 6-42173622-C-T is Benign according to our data. Variant chr6-42173622-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 196267.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr6-42173622-C-T is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=0.17 with no splicing effect.

BS2

High AC in GnomAd4 at 546 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GUCA1A	NM_001384910.1 link	c.9C>T	p.Asn3Asn	synonymous_variant	1/4	ENST00000372958.2	NP_001371839.1
GUCA1ANB-GUCA1A	NM_000409.5 link	c.9C>T	p.Asn3Asn	synonymous_variant	3/6		NP_000400.2	P43080
GUCA1ANB-GUCA1A	NM_001319061.2 link	c.9C>T	p.Asn3Asn	synonymous_variant	3/6		NP_001305990.1	P43080
GUCA1ANB-GUCA1A	NM_001319062.2 link	c.9C>T	p.Asn3Asn	synonymous_variant	2/5		NP_001305991.1	P43080B2R9P6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GUCA1A	ENST00000372958.2 link	c.9C>T	p.Asn3Asn	synonymous_variant	1/4	1	NM_001384910.1	ENSP00000362049.1		P43080
ENSG00000290147	ENST00000654459.1 link	c.9C>T	p.Asn3Asn	synonymous_variant	2/5			ENSP00000499539.1

Frequencies

GnomAD3 genomes

AF:

0.00358

AC:

545

AN:

152204

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0124

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00164

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:

0.0000294

Gnomad OTH

AF:

0.00239

GnomAD3 exomes

AF:

0.000812

AC:

204

AN:

251326

Hom.:

AF XY:

0.000501

AC XY:

AN XY:

135848

show subpopulations

Gnomad AFR exome

AF:

0.0114

Gnomad AMR exome

AF:

0.000202

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000653

Gnomad FIN exome

AF:

0.0000463

Gnomad NFE exome

AF:

0.0000616

Gnomad OTH exome

AF:

0.000326

GnomAD4 exome

AF:

0.000393

AC:

574

AN:

1461326

Hom.:

Cov.:

AF XY:

0.000319

AC XY:

232

AN XY:

727006

show subpopulations

Gnomad4 AFR exome

AF:

0.0130

Gnomad4 AMR exome

AF:

0.000335

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000139

Gnomad4 FIN exome

AF:

0.0000187

Gnomad4 NFE exome

AF:

0.0000603

Gnomad4 OTH exome

AF:

0.000696

GnomAD4 genome

AF:

0.00358

AC:

546

AN:

152322

Hom.:

Cov.:

AF XY:

0.00342

AC XY:

255

AN XY:

74488

show subpopulations

Gnomad4 AFR

AF:

0.0124

Gnomad4 AMR

AF:

0.00163

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000294

Gnomad4 OTH

AF:

0.00237

Alfa

AF:

0.00171

Hom.:

Bravo

AF:

0.00399

Asia WGS

AF:

0.000577

AC:

AN:

3478

EpiCase

AF:

0.0000545

EpiControl

AF:

0.00

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

Eurofins Ntd Llc (ga)

May 14, 2014

- -

Cone dystrophy 3

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 09, 2017

This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases allowed determination this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign. -

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 25, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.53

CADD

Benign

9.0

DANN

Benign

0.57

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over