1-101830677-A-C

Position:

• chr1-101830677-A-C

Variant summary

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

The NM_058170.4(OLFM3):​c.367T>G​(p.Phe123Val) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: OLFM3 NM_058170.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 9.27

Genes affected

OLFM3 (HGNC:17990): (olfactomedin 3) Predicted to be involved in eye photoreceptor cell development. Predicted to be located in Golgi apparatus; extracellular space; and synapse. Predicted to be part of AMPA glutamate receptor complex. [provided by Alliance of Genome Resources, Apr 2022]

OLFM3 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
OLFM3	NM_058170.4	c.367T>G	p.Phe123Val	missense_variant	3/6	ENST00000370103.9	NP_477518.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
OLFM3	ENST00000370103.9	c.367T>G	p.Phe123Val	missense_variant	3/6	1	NM_058170.4	ENSP00000359121.5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

May 15, 2024

The c.367T>G (p.F123V) alteration is located in exon 3 (coding exon 3) of the OLFM3 gene. This alteration results from a T to G substitution at nucleotide position 367, causing the phenylalanine (F) at amino acid position 123 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.37
BayesDel_addAF	Pathogenic	0.19	D
BayesDel_noAF	Uncertain	0.040
CADD	Uncertain	25
DANN	Uncertain	0.98
DEOGEN2	Benign	0.082	.;.;T
Eigen	Uncertain	0.40
Eigen_PC	Uncertain	0.50
FATHMM_MKL	Pathogenic	1.0	D
LIST_S2	Uncertain	0.94	D;D;D
M_CAP	Benign	0.0071	T
MetaRNN	Uncertain	0.65	D;D;D
MetaSVM	Benign	-0.93	T
MutationAssessor	Uncertain	2.0	.;.;M
PrimateAI	Pathogenic	0.82	D
PROVEAN	Benign	-1.6	N;D;N
REVEL	Uncertain	0.33
Sift	Benign	0.089	T;D;T
Sift4G	Uncertain	0.052	T;T;T
Polyphen		0.48	.;.;P
Vest4		0.82
MutPred		0.38		.;.;Gain of ubiquitination at K141 (P = 0.086);
MVP		0.63
MPC		0.59
ClinPred		0.87	D
GERP RS		5.4
Varity_R		0.29
gMVP		0.63

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: chr1-102296233;