NM_001379270.1:c.1994T>C

Variant names:

• chr4-47936488-A-G
• NM_001379270.1:c.1994T>C

Variant summary

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

The NM_001379270.1(CNGA1):​c.1994T>C​(p.Leu665Pro) 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. 14/21 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: CNGA1 NM_001379270.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.81

Genes affected

CNGA1 (HGNC:2148): (cyclic nucleotide gated channel subunit alpha 1) The protein encoded by this gene is involved in phototransduction. Along with another protein, the encoded protein forms a cGMP-gated cation channel in the plasma membrane, allowing depolarization of rod photoreceptors. This represents the last step in the phototransduction pathway. Defects in this gene are a cause of retinitis pigmentosa autosomal recessive (ARRP) disease. Multiple transcript variants have been found for this gene. [provided by RefSeq, Oct 2019]

NIPAL1 (HGNC:27194): (NIPA like domain containing 1) Predicted to enable magnesium ion transmembrane transporter activity. Predicted to be involved in magnesium ion transport. Predicted to be integral component of membrane. Predicted to be active in membrane. [provided by Alliance of Genome Resources, Apr 2022]

LOC101927157 (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=0.12559506).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CNGA1	NM_001379270.1	c.1994T>C	p.Leu665Pro	missense_variant	Exon 11 of 11	ENST00000514170.7	NP_001366199.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CNGA1	ENST00000514170.7	c.1994T>C	p.Leu665Pro	missense_variant	Exon 11 of 11	5	NM_001379270.1	ENSP00000426862.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

Retinal dystrophy Uncertain:1

Oct 01, 2023

Dept Of Ophthalmology, Nagoya University

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: research

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.23
BayesDel_addAF	Uncertain	0.040	T
BayesDel_noAF	Benign	-0.18
CADD	Benign	21
DANN	Benign	0.95
DEOGEN2	Benign	0.062	.;T;.;T;T
Eigen	Benign	-0.31
Eigen_PC	Benign	-0.17
FATHMM_MKL	Benign	0.48	N
LIST_S2	Benign	0.59	.;.;T;T;.
M_CAP	Uncertain	0.094	D
MetaRNN	Benign	0.13	T;T;T;T;T
MetaSVM	Uncertain	0.071	D
MutationAssessor	Benign	1.7	.;L;.;L;L
PrimateAI	Benign	0.35	T
PROVEAN	Benign	-0.93	N;N;.;N;N
REVEL	Benign	0.28
Sift	Benign	0.093	T;T;.;T;T
Sift4G	Benign	0.22	T;T;T;T;T
Polyphen		0.0	.;B;.;B;B
Vest4		0.30
MutPred		0.46		.;Gain of disorder (P = 0.0098);.;Gain of disorder (P = 0.0098);Gain of disorder (P = 0.0098);
MVP		0.92
MPC		0.18
ClinPred		0.18	T
GERP RS		4.5
Varity_R		0.18
gMVP		0.22

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: chr4-47938505;