6-42173622-C-T

Variant names:

• chr6-42173622-C-T
• rs116114043
• NM_001384910.1:c.9C>T

Variant summary

Our verdict is Benign. The variant received -17 ACMG points: 0P and 17B. BP4_Strong BP6_Very_Strong BP7 BS2

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
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 0.170
• Publications: 0 publications found

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: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]

ACMG classification

Our verdict: Benign. The variant received -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 Benign/Likely_benign. ClinVar VariationId is 196267.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=0.17 with no splicing effect.
• BS2: High AC in GnomAd4 at 546 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001384910.1. 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
	GUCA1A	NM_001384910.1	MANE Select	c.9C>T	p.Asn3Asn	synonymous	Exon 1 of 4	NP_001371839.1	P43080
	GUCA1ANB-GUCA1A	NM_000409.5		c.9C>T	p.Asn3Asn	synonymous	Exon 3 of 6	NP_000400.2
	GUCA1ANB-GUCA1A	NM_001319061.2		c.9C>T	p.Asn3Asn	synonymous	Exon 3 of 6	NP_001305990.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GUCA1A	ENST00000372958.2	TSL:1 MANE Select	c.9C>T	p.Asn3Asn	synonymous	Exon 1 of 4	ENSP00000362049.1	P43080
	GUCA1ANB-GUCA1A	ENST00000654459.1		c.9C>T	p.Asn3Asn	synonymous	Exon 2 of 5	ENSP00000499539.1
	GUCA1ANB-GUCA1A	ENST00000703265.1		n.*244C>T		non_coding_transcript_exon	Exon 3 of 4	ENSP00000515250.1	A6PVH5

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

GnomAD2 exomes AF: 0.000812 AC: 204 AN: 251326 AF XY: 0.000501

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 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

African (AFR) AF: 0.0130 AC: 434 AN: 33458

American (AMR) AF: 0.000335 AC: 15 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26134

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.000139 AC: 12 AN: 86242

European-Finnish (FIN) AF: 0.0000187 AC: 1 AN: 53382

Middle Eastern (MID) AF: 0.000530 AC: 3 AN: 5660

European-Non Finnish (NFE) AF: 0.0000603 AC: 67 AN: 1111660

Other (OTH) AF: 0.000696 AC: 42 AN: 60366

GnomAD4 genome AF: 0.00358 AC: 546 AN: 152322 Hom.: 2 Cov.: 33 AF XY: 0.00342 AC XY: 255 AN XY: 74488

African (AFR) AF: 0.0124 AC: 514 AN: 41574

American (AMR) AF: 0.00163 AC: 25 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5186

South Asian (SAS) AF: 0.00 AC: 0 AN: 4830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10622

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000294 AC: 2 AN: 68014

Other (OTH) AF: 0.00237 AC: 5 AN: 2114

Alfa AF: 0.00172 Hom.: 0

Bravo AF: 0.00399

Asia WGS AF: 0.000577 AC: 2 AN: 3478

EpiCase AF: 0.0000545

EpiControl AF: 0.00

ClinVar

ClinVar submissions

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	1	Cone dystrophy 3 (1)
-	-	1	not provided (1)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.53
CADD	Benign	9.0
DANN	Benign	0.57
PhyloP100		0.17
PromoterAI		-0.054	Neutral
Mutation Taster		=99/1	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

dbSNP: rs116114043; hg19: chr6-42141360;