rs370499285

Variant names:

• chr1-241634163-T-C
• rs370499285
• NM_001381853.1:c.1604A>G

Your query was ambiguous. Multiple possible variants found:

• chr1-241634163-T-C
• chr1-241634163-T-A

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001381853.1(CHML):​c.1604A>G​(p.Glu535Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000329 in 152,198 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: 𝑓 0.000033 (0 hom., cov: 32)
• Consequence: CHML NM_001381853.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.64
• Publications: 0 publications found

Genes affected

CHML (HGNC:1941): (CHM like Rab escort protein) The product of the CHML gene supports geranylgeranylation of most Rab proteins and may substitute for REP-1 in tissues other than retina. CHML is localized close to the gene for Usher syndrome type II. [provided by RefSeq, Jul 2008]

OPN3 (HGNC:14007): (opsin 3) Opsins are members of the guanine nucleotide-binding protein (G protein)-coupled receptor superfamily. In addition to the visual opsins, mammals possess several photoreceptive non-visual opsins that are expressed in extraocular tissues. This gene, opsin 3, is strongly expressed in brain and testis and weakly expressed in liver, placenta, heart, lung, skeletal muscle, kidney, and pancreas. The gene may also be expressed in the retina. The protein has the canonical features of a photoreceptive opsin protein. [provided by RefSeq, Jul 2008]

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.4175074).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001381853.1. 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
	CHML	NM_001381853.1	MANE Select	c.1604A>G	p.Glu535Gly	missense	Exon 2 of 2	NP_001368782.1	P26374
	OPN3	NM_014322.3	MANE Select	c.373+5719A>G		intron	N/A	NP_055137.2	Q9H1Y3-1
	CHML	NM_001381854.1		c.1604A>G	p.Glu535Gly	missense	Exon 2 of 2	NP_001368783.1	P26374

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CHML	ENST00000366553.3	TSL:2 MANE Select	c.1604A>G	p.Glu535Gly	missense	Exon 2 of 2	ENSP00000355511.1	P26374
	OPN3	ENST00000366554.3	TSL:1 MANE Select	c.373+5719A>G		intron	N/A	ENSP00000355512.2	Q9H1Y3-1
	OPN3	ENST00000469376.5	TSL:1	n.373+5719A>G		intron	N/A	ENSP00000490012.1	Q6P5W7

Frequencies

GnomAD3 genomes AF: 0.0000329 AC: 5 AN: 152198 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000121

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 Cov.: 33

GnomAD4 genome AF: 0.0000329 AC: 5 AN: 152198 Hom.: 0 Cov.: 32 AF XY: 0.0000403 AC XY: 3 AN XY: 74372

African (AFR) AF: 0.000121 AC: 5 AN: 41450

American (AMR) AF: 0.00 AC: 0 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5198

South Asian (SAS) AF: 0.00 AC: 0 AN: 4832

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10628

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68026

Other (OTH) AF: 0.00 AC: 0 AN: 2092

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000340

ESP6500AA AF: 0.000227 AC: 1

ESP6500EA AF: 0.000116 AC: 1

ExAC AF: 0.00000824 AC: 1

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	0.084
BayesDel_addAF	Uncertain	0.086	D
BayesDel_noAF	Benign	-0.11
CADD	Benign	21
DANN	Uncertain	1.0
DEOGEN2	Benign	0.19	T
Eigen	Benign	0.0091
Eigen_PC	Benign	-0.14
FATHMM_MKL	Benign	0.45	N
LIST_S2	Benign	0.80	T
M_CAP	Uncertain	0.26	D
MetaRNN	Benign	0.42	T
MetaSVM	Uncertain	0.20	D
MutationAssessor	Pathogenic	3.2	M
PhyloP100		1.6
PrimateAI	Benign	0.40	T
PROVEAN	Uncertain	-2.5	D
REVEL	Uncertain	0.58
Sift	Uncertain	0.0030	D
Sift4G	Uncertain	0.013	D
Polyphen		0.99	D
Vest4		0.18
MVP		0.92
MPC		0.17
ClinPred		0.88	D
GERP RS		3.4
Varity_R		0.11
gMVP		0.32
Mutation Taster		=87/13	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: rs370499285; hg19: chr1-241797465;