chr6-42173654-G-C

Position:

• chr6-42173654-G-C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001384910.1(GUCA1A):​c.41G>C​(p.Ser14Thr) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Synonymous variant affecting the same amino acid position (i.e. S14S) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 33)
• Consequence: GUCA1A NM_001384910.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.31

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 Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.17917371).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GUCA1A	NM_001384910.1	c.41G>C	p.Ser14Thr	missense_variant	1/4	ENST00000372958.2
GUCA1ANB-GUCA1A	NM_001319061.2	c.41G>C	p.Ser14Thr	missense_variant	3/6
GUCA1ANB-GUCA1A	NM_000409.5	c.41G>C	p.Ser14Thr	missense_variant	3/6
GUCA1ANB-GUCA1A	NM_001319062.2	c.41G>C	p.Ser14Thr	missense_variant	2/5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GUCA1A	ENST00000372958.2	c.41G>C	p.Ser14Thr	missense_variant	1/4	1	NM_001384910.1	P1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

Retinal dystrophy Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Blueprint Genetics

Aug 28, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.084
BayesDel_addAF	Benign	-0.045	T
BayesDel_noAF	Benign	-0.30
CADD	Benign	21
DANN	Benign	0.92
DEOGEN2	Benign	0.094	.;.;T;T;T
Eigen	Benign	-0.29
Eigen_PC	Benign	-0.042
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Benign	0.66	.;T;.;.;T
M_CAP	Benign	0.010	T
MetaRNN	Benign	0.18	T;T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.72	.;.;N;N;N
MutationTaster	Benign	1.0	D;D;D;D
PrimateAI	Uncertain	0.66	T
PROVEAN	Benign	-0.98	N;.;N;N;N
REVEL	Benign	0.075
Sift	Benign	0.95	T;.;T;T;T
Sift4G	Benign	1.0	T;T;T;T;T
Polyphen		0.035	.;.;B;B;B
Vest4		0.30, 0.095, 0.10, 0.10
MutPred		0.24		Loss of phosphorylation at S14 (P = 0.0665);.;Loss of phosphorylation at S14 (P = 0.0665);Loss of phosphorylation at S14 (P = 0.0665);Loss of phosphorylation at S14 (P = 0.0665);
MVP		0.73
MPC		0.24
ClinPred		0.68	D
GERP RS		5.1
Varity_R		0.19
gMVP		0.51

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: rs1767870135; hg19: chr6-42141392;