3-108953566-G-T

Variant names:

• chr3-108953566-G-T
• NM_005459.4:c.197C>A

Variant summary

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

The NM_005459.4(GUCA1C):​c.197C>A​(p.Thr66Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000698 in 1,431,824 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict 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: 32)
  • Exomes 𝑓: 7.0e-7 (0 hom.)
• Consequence: GUCA1C NM_005459.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.904

Genes affected

GUCA1C (HGNC:4680): (guanylate cyclase activator 1C) Predicted to enable calcium ion binding activity and calcium sensitive guanylate cyclase activator activity. Predicted to be involved in signal transduction. Predicted to be located in photoreceptor disc membrane. [provided by Alliance of Genome Resources, Apr 2022]

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=0.109331995).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GUCA1C	NM_005459.4	c.197C>A	p.Thr66Lys	missense_variant	Exon 1 of 4	ENST00000261047.8	NP_005450.3
GUCA1C	NM_001363884.1	c.197C>A	p.Thr66Lys	missense_variant	Exon 1 of 4		NP_001350813.1
GUCA1C	XM_011513334.3	c.-49+1576C>A		intron_variant	Intron 1 of 3		XP_011511636.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GUCA1C	ENST00000261047.8	c.197C>A	p.Thr66Lys	missense_variant	Exon 1 of 4	1	NM_005459.4	ENSP00000261047.3
GUCA1C	ENST00000393963.7	c.197C>A	p.Thr66Lys	missense_variant	Exon 1 of 4	1		ENSP00000377535.3
GUCA1C	ENST00000471108.1	c.197C>A	p.Thr66Lys	missense_variant	Exon 1 of 3	2		ENSP00000417761.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.98e-7 AC: 1 AN: 1431824 Hom.: 0 Cov.: 28 AF XY: 0.00000140 AC XY: 1 AN XY: 714216

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 9.22e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.088
BayesDel_addAF	Benign	-0.27	T
BayesDel_noAF	Benign	-0.63
CADD	Benign	7.0
DANN	Benign	0.67
DEOGEN2	Benign	0.0034	.;T;.
Eigen	Benign	-1.0
Eigen_PC	Benign	-0.90
FATHMM_MKL	Benign	0.49	N
LIST_S2	Benign	0.67	T;T;T
M_CAP	Benign	0.0048	T
MetaRNN	Benign	0.11	T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.17	.;N;.
PrimateAI	Benign	0.24	T
PROVEAN	Benign	-0.49	N;N;N
REVEL	Benign	0.077
Sift	Benign	1.0	T;T;T
Sift4G	Benign	0.15	T;T;T
Polyphen		0.032	B;B;.
Vest4		0.087
MutPred		0.40		Gain of ubiquitination at T66 (P = 0.0238);Gain of ubiquitination at T66 (P = 0.0238);Gain of ubiquitination at T66 (P = 0.0238);
MVP		0.21
MPC		0.030
ClinPred		0.17	T
GERP RS		-4.9
Varity_R		0.32
gMVP		0.37

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr3-108672413;