3-108916159-A-G

Variant names:

• chr3-108916159-A-G
• rs1946508819
• NM_005459.4:c.410T>C

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_005459.4(GUCA1C):​c.410T>C​(p.Leu137Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 17/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: GUCA1C NM_005459.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.37
• Publications: 0 publications found

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

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.21947685).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005459.4. 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
	GUCA1C	NM_005459.4	MANE Select	c.410T>C	p.Leu137Ser	missense	Exon 3 of 4	NP_005450.3
	GUCA1C	NM_001363884.1		c.410T>C	p.Leu137Ser	missense	Exon 3 of 4	NP_001350813.1	C9JNI2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GUCA1C	ENST00000261047.8	TSL:1 MANE Select	c.410T>C	p.Leu137Ser	missense	Exon 3 of 4	ENSP00000261047.3	O95843-1
	GUCA1C	ENST00000393963.7	TSL:1	c.410T>C	p.Leu137Ser	missense	Exon 3 of 4	ENSP00000377535.3	C9JNI2
	GUCA1C	ENST00000471108.1	TSL:2	c.410T>C	p.Leu137Ser	missense	Exon 3 of 3	ENSP00000417761.1	C9J7M7

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.16
BayesDel_addAF	Benign	-0.069	T
BayesDel_noAF	Benign	-0.34
CADD	Benign	21
DANN	Benign	0.96
DEOGEN2	Benign	0.036	T
Eigen	Benign	-0.31
Eigen_PC	Benign	-0.34
FATHMM_MKL	Benign	0.26	N
LIST_S2	Benign	0.72	T
M_CAP	Benign	0.023	T
MetaRNN	Benign	0.22	T
MetaSVM	Benign	-0.89	T
MutationAssessor	Benign	1.2	L
PhyloP100		2.4
PrimateAI	Benign	0.28	T
PROVEAN	Benign	-1.0	N
REVEL	Benign	0.10
Sift	Benign	0.10	T
Sift4G	Benign	0.41	T
Polyphen		0.43	B
Vest4		0.25
MutPred		0.40		Loss of stability (P = 0.0123)
MVP		0.80
MPC		0.13
ClinPred		0.47	T
GERP RS		2.9
Varity_R		0.21
gMVP		0.55
Mutation Taster		=85/15	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: rs1946508819; hg19: chr3-108635006;