6-42173531-G-C

Variant names:

• chr6-42173531-G-C
• rs9471793
• NM_001384910.1:c.-83G>C

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001384910.1(GUCA1A):​c.-83G>C variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000309 in 971,256 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000031 (0 hom.)
• Consequence: GUCA1A NM_001384910.1 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.45
• Publications: 6 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).

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.-83G>C		5_prime_UTR	Exon 1 of 4	NP_001371839.1	P43080
	GUCA1ANB-GUCA1A	NM_000409.5		c.-83G>C		5_prime_UTR	Exon 3 of 6	NP_000400.2
	GUCA1ANB-GUCA1A	NM_001319061.2		c.-83G>C		5_prime_UTR	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.-83G>C		5_prime_UTR	Exon 1 of 4	ENSP00000362049.1	P43080
	GUCA1ANB-GUCA1A	ENST00000654459.1		c.-83G>C		5_prime_UTR	Exon 2 of 5	ENSP00000499539.1
	GUCA1ANB-GUCA1A	ENST00000703265.1		n.*153G>C		non_coding_transcript_exon	Exon 3 of 4	ENSP00000515250.1	A6PVH5

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000309 AC: 3 AN: 971256 Hom.: 0 Cov.: 13 AF XY: 0.00000596 AC XY: 3 AN XY: 503478

African (AFR) AF: 0.00 AC: 0 AN: 24082

American (AMR) AF: 0.00 AC: 0 AN: 43240

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 23054

East Asian (EAS) AF: 0.00 AC: 0 AN: 37348

South Asian (SAS) AF: 0.0000395 AC: 3 AN: 75888

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 48526

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3230

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 671814

Other (OTH) AF: 0.00 AC: 0 AN: 44074

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 655

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	0.24
DANN	Benign	0.39
PhyloP100		-1.5
PromoterAI		-0.029	Neutral

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: rs9471793; hg19: chr6-42141269;