2-233309254-G-T

Variant names:

• chr2-233309254-G-T
• rs371502229
• NM_000541.5:c.65G>T

Variant summary

Our verdict is Likely benign. Variant got -1 ACMG points: 0P and 1B. BP4

The NM_000541.5(SAG):​c.65G>T​(p.Arg22Leu) variant causes a missense change. The variant allele was found at a frequency of 0.0000093 in 1,613,050 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: 𝑓 0.0000066 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0000096 (0 hom.)
• Consequence: SAG NM_000541.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.10

Genes affected

SAG (HGNC:10521): (S-antigen visual arrestin) Members of arrestin/beta-arrestin protein family are thought to participate in agonist-mediated desensitization of G-protein-coupled receptors and cause specific dampening of cellular responses to stimuli such as hormones, neurotransmitters, or sensory signals. S-arrestin, also known as S-antigen, is a major soluble photoreceptor protein that is involved in desensitization of the photoactivated transduction cascade. It is expressed in the retina and the pineal gland and inhibits coupling of rhodopsin to transducin in vitro. Additionally, S-arrestin is highly antigenic, and is capable of inducing experimental autoimmune uveoretinitis. Mutations in this gene have been associated with Oguchi disease, a rare autosomal recessive form of night blindness. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Likely_benign. Variant got -1 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.305618).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SAG	NM_000541.5	c.65G>T	p.Arg22Leu	missense_variant	Exon 2 of 16	ENST00000409110.6	NP_000532.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SAG	ENST00000409110.6	c.65G>T	p.Arg22Leu	missense_variant	Exon 2 of 16	5	NM_000541.5	ENSP00000386444.1

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152116 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000241

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.00000958 AC: 14 AN: 1460934 Hom.: 0 Cov.: 29 AF XY: 0.0000124 AC XY: 9 AN XY: 726774

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: 0.0000126

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.00000657 AC: 1 AN: 152116 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 74318

Gnomad4 AFR AF: 0.0000241

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00

Gnomad4 OTH AF: 0.00

EpiCase AF: 0.0000545

EpiControl AF: 0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.69
BayesDel_addAF	Benign	-0.062	T
BayesDel_noAF	Benign	-0.33
CADD	Pathogenic	28
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.42	.;T;.
Eigen	Uncertain	0.50
Eigen_PC	Uncertain	0.50
FATHMM_MKL	Uncertain	0.93	D
M_CAP	Benign	0.0040	T
MetaRNN	Benign	0.31	T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.1	.;M;.
PrimateAI	Uncertain	0.56	T
PROVEAN	Benign	-2.1	N;N;D
REVEL	Benign	0.075
Sift	Uncertain	0.024	D;D;T
Sift4G	Uncertain	0.043	D;D;T
Polyphen		0.99	.;D;.
Vest4		0.64
MutPred		0.41		Loss of MoRF binding (P = 0.0074);Loss of MoRF binding (P = 0.0074);Loss of MoRF binding (P = 0.0074);
MVP		0.44
MPC		0.51
ClinPred		0.96	D
GERP RS		4.5
Varity_R		0.29
gMVP		0.31

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: rs371502229; hg19: chr2-234217900; COSMIC: COSV68591185;