1-101825080-G-A

Position:

• chr1-101825080-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_058170.4(OLFM3):​c.538C>T​(p.His180Tyr) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/21 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: OLFM3 NM_058170.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.85

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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.35670426).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
OLFM3	NM_058170.4	c.538C>T	p.His180Tyr	missense_variant	4/6	ENST00000370103.9	NP_477518.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
OLFM3	ENST00000370103.9	c.538C>T	p.His180Tyr	missense_variant	4/6	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

Apr 18, 2023

The c.538C>T (p.H180Y) alteration is located in exon 4 (coding exon 4) of the OLFM3 gene. This alteration results from a C to T substitution at nucleotide position 538, causing the histidine (H) at amino acid position 180 to be replaced by a tyrosine (Y). 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	Benign	0.10
BayesDel_addAF	Benign	-0.048	T
BayesDel_noAF	Benign	-0.31
CADD	Benign	22
DANN	Uncertain	0.99
DEOGEN2	Benign	0.058	.;.;T
Eigen	Benign	-0.16
Eigen_PC	Benign	0.054
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.92	D;D;D
M_CAP	Benign	0.026	D
MetaRNN	Benign	0.36	T;T;T
MetaSVM	Benign	-0.61	T
MutationAssessor	Benign	0.28	.;.;N
PrimateAI	Uncertain	0.73	T
PROVEAN	Benign	-1.4	N;N;N
REVEL	Benign	0.28
Sift	Benign	0.096	T;T;T
Sift4G	Benign	0.32	T;T;T
Polyphen		0.0	.;.;B
Vest4		0.41
MutPred		0.39		.;.;Gain of phosphorylation at H200 (P = 0.0809);
MVP		0.88
MPC		0.40
ClinPred		0.92	D
GERP RS		5.9
Varity_R		0.10
gMVP		0.56

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: rs1654795039; hg19: chr1-102290636;