6-42173622-C-T

Position:

• chr6-42173622-C-T

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BS1 BS2

The NM_001384910.1(GUCA1A):​c.9C>T​(p.Asn3=) 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
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 0.170

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]

GUCA1ANB-GUCA1A (HGNC:):

ACMG classification

Verdict is Benign. Variant got -21 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.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00358 (546/152322) while in subpopulation AFR AF= 0.0124 (514/41574). AF 95% confidence interval is 0.0115. There are 2 homozygotes in gnomad4. There are 255 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
• 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	c.9C>T	p.Asn3=	synonymous_variant	1/4	ENST00000372958.2	NP_001371839.1
GUCA1ANB-GUCA1A	NM_001319061.2	c.9C>T	p.Asn3=	synonymous_variant	3/6		NP_001305990.1
GUCA1ANB-GUCA1A	NM_000409.5	c.9C>T	p.Asn3=	synonymous_variant	3/6		NP_000400.2
GUCA1ANB-GUCA1A	NM_001319062.2	c.9C>T	p.Asn3=	synonymous_variant	2/5		NP_001305991.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GUCA1A	ENST00000372958.2	c.9C>T	p.Asn3=	synonymous_variant	1/4	1	NM_001384910.1	ENSP00000362049	P1

Frequencies

GnomAD3 genomes AF: 0.00358 AC: 545 AN: 152204 Hom.: 2 Cov.: 33

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.: 1 AF XY: 0.000501 AC XY: 68 AN XY: 135848

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.: 5 Cov.: 31 AF XY: 0.000319 AC XY: 232 AN XY: 727006

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.: 2 Cov.: 33 AF XY: 0.00342 AC XY: 255 AN XY: 74488

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.: 0

Bravo AF: 0.00399

Asia WGS AF: 0.000577 AC: 2 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

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

Other links and lift over

dbSNP: rs116114043; hg19: chr6-42141360;