chr1-101825101-C-T

Position:

• chr1-101825101-C-T

Variant summary

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

The NM_058170.4(OLFM3):​c.517G>A​(p.Ala173Thr) 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: OLFM3 NM_058170.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.16

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=0.4082043).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
OLFM3	NM_058170.4	c.517G>A	p.Ala173Thr	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.517G>A	p.Ala173Thr	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

Oct 24, 2024

The c.517G>A (p.A173T) alteration is located in exon 4 (coding exon 4) of the OLFM3 gene. This alteration results from a G to A substitution at nucleotide position 517, causing the alanine (A) at amino acid position 173 to be replaced by a threonine (T). 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	0.091
BayesDel_addAF	Pathogenic	0.18	D
BayesDel_noAF	Uncertain	0.020
CADD	Uncertain	23
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.022	.;.;T
Eigen	Uncertain	0.27
Eigen_PC	Uncertain	0.38
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.96	D;D;D
M_CAP	Benign	0.043	D
MetaRNN	Benign	0.41	T;T;T
MetaSVM	Uncertain	0.031	D
MutationAssessor	Uncertain	2.3	.;.;M
PrimateAI	Uncertain	0.70	T
PROVEAN	Benign	0.17	N;N;N
REVEL	Uncertain	0.36
Sift	Benign	0.23	T;D;T
Sift4G	Uncertain	0.014	D;D;D
Polyphen		0.90	.;.;P
Vest4		0.48
MutPred		0.45		.;.;Gain of phosphorylation at A193 (P = 0.0758);
MVP		0.92
MPC		0.40
ClinPred		0.76	D
GERP RS		5.7
Varity_R		0.16
gMVP		0.58

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: chr1-102290657;