chr6-42179364-C-T

Variant names:

• chr6-42179364-C-T
• rs34925828
• NM_001384910.1:c.567C>T

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BS1 BS2

The NM_001384910.1(GUCA1A):​c.567C>T​(p.Asp189Asp) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00249 in 1,611,224 control chromosomes in the GnomAD database, including 55 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.012 (31 hom., cov: 32)
  • Exomes 𝑓: 0.0015 (24 hom.)
• Consequence: GUCA1A NM_001384910.1 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:7
• Conservation: PhyloP100: -1.98
• Publications: 1 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 -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BP6: Variant 6-42179364-C-T is Benign according to our data. Variant chr6-42179364-C-T is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 256032.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-1.98 with no splicing effect.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.0119 (1812/152304) while in subpopulation AFR AF = 0.0394 (1639/41552). AF 95% confidence interval is 0.0379. There are 31 homozygotes in GnomAd4. There are 839 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High AC in GnomAd4 at 1812 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.567C>T	p.Asp189Asp	synonymous	Exon 4 of 4	NP_001371839.1	P43080
	GUCA1ANB-GUCA1A	NM_000409.5		c.567C>T	p.Asp189Asp	synonymous	Exon 6 of 6	NP_000400.2
	GUCA1ANB-GUCA1A	NM_001319061.2		c.567C>T	p.Asp189Asp	synonymous	Exon 6 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.567C>T	p.Asp189Asp	synonymous	Exon 4 of 4	ENSP00000362049.1	P43080
	GUCA1ANB-GUCA1A	ENST00000654459.1		c.567C>T	p.Asp189Asp	synonymous	Exon 5 of 5	ENSP00000499539.1
	GUCA1A	ENST00000679182.1		c.348C>T	p.Asp116Asp	synonymous	Exon 3 of 3	ENSP00000504837.1	A0A7I2V6E2

Frequencies

GnomAD3 genomes AF: 0.0119 AC: 1806 AN: 152186 Hom.: 32 Cov.: 32

Gnomad AFR AF: 0.0394

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00700

Gnomad ASJ AF: 0.00115

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.000353

Gnomad OTH AF: 0.0167

GnomAD2 exomes AF: 0.00337 AC: 827 AN: 245350 AF XY: 0.00257

Gnomad AFR exome AF: 0.0389

Gnomad AMR exome AF: 0.00364

Gnomad ASJ exome AF: 0.000305

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000580

Gnomad OTH exome AF: 0.00449

GnomAD4 exome AF: 0.00150 AC: 2195 AN: 1458920 Hom.: 24 Cov.: 31 AF XY: 0.00134 AC XY: 969 AN XY: 725416

African (AFR) AF: 0.0391 AC: 1307 AN: 33414

American (AMR) AF: 0.00390 AC: 173 AN: 44414

Ashkenazi Jewish (ASJ) AF: 0.000615 AC: 16 AN: 26014

East Asian (EAS) AF: 0.00 AC: 0 AN: 39626

South Asian (SAS) AF: 0.0000931 AC: 8 AN: 85966

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53156

Middle Eastern (MID) AF: 0.00869 AC: 50 AN: 5754

European-Non Finnish (NFE) AF: 0.000362 AC: 402 AN: 1110326

Other (OTH) AF: 0.00397 AC: 239 AN: 60250

GnomAD4 genome AF: 0.0119 AC: 1812 AN: 152304 Hom.: 31 Cov.: 32 AF XY: 0.0113 AC XY: 839 AN XY: 74474

African (AFR) AF: 0.0394 AC: 1639 AN: 41552

American (AMR) AF: 0.00699 AC: 107 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.00115 AC: 4 AN: 3470

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

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4826

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10618

Middle Eastern (MID) AF: 0.00680 AC: 2 AN: 294

European-Non Finnish (NFE) AF: 0.000353 AC: 24 AN: 68030

Other (OTH) AF: 0.0166 AC: 35 AN: 2112

Alfa AF: 0.0101 Hom.: 22

Bravo AF: 0.0132

Asia WGS AF: 0.00520 AC: 18 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	not provided (3)
-	-	1	Cone dystrophy (1)
-	-	1	Cone dystrophy 3 (1)
-	-	1	not specified (1)
-	-	1	Retinitis Pigmentosa, Dominant (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	0.24
DANN	Benign	0.61
PhyloP100		-2.0
Mutation Taster		=100/0	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: rs34925828; hg19: chr6-42147102;