9-135106794-C-A

Position:

• chr9-135106794-C-A

Variant summary

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

The NM_001282611.2(OLFM1):​c.722C>A​(p.Thr241Asn) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 34)
• Consequence: OLFM1 NM_001282611.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.97

Genes affected

OLFM1 (HGNC:17187): (olfactomedin 1) This gene product shares extensive sequence similarity with the rat neuronal olfactomedin-related ER localized protein. While the exact function of the encoded protein is not known, its abundant expression in brain suggests that it may have an essential role in nerve tissue. Several alternatively spliced transcripts encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

OLFM1 (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
OLFM1	NM_001282611.2	c.722C>A	p.Thr241Asn	missense_variant	5/6	ENST00000371793.8	NP_001269540.1
OLFM1	NM_014279.5	c.668C>A	p.Thr223Asn	missense_variant	5/6		NP_055094.1
OLFM1	NM_001282612.1	c.641C>A	p.Thr214Asn	missense_variant	5/6		NP_001269541.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
OLFM1	ENST00000371793.8	c.722C>A	p.Thr241Asn	missense_variant	5/6	3	NM_001282611.2	ENSP00000360858.3

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 34

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

Nov 17, 2023

The c.668C>A (p.T223N) alteration is located in exon 5 (coding exon 5) of the OLFM1 gene. This alteration results from a C to A substitution at nucleotide position 668, causing the threonine (T) at amino acid position 223 to be replaced by an asparagine (N). 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	Uncertain	0.11	D
BayesDel_noAF	Uncertain	-0.080
CADD	Uncertain	26
DANN	Uncertain	0.99
DEOGEN2	Uncertain	0.66	.;.;D;T
Eigen	Uncertain	0.66
Eigen_PC	Uncertain	0.63
FATHMM_MKL	Uncertain	0.97	D
LIST_S2	Uncertain	0.96	D;D;D;D
M_CAP	Uncertain	0.23	D
MetaRNN	Uncertain	0.57	D;D;D;D
MetaSVM	Uncertain	0.74	D
MutationAssessor	Uncertain	2.0	.;.;M;.
MutationTaster	Benign	1.0	D;D;D
PrimateAI	Pathogenic	0.83	D
PROVEAN	Benign	-0.91	N;N;N;N
REVEL	Uncertain	0.55
Sift	Uncertain	0.0020	D;D;D;T
Sift4G	Benign	0.078	T;T;T;D
Polyphen		1.0	.;.;D;.
Vest4		0.85
MutPred		0.37		.;.;Loss of phosphorylation at T241 (P = 0.0455);.;
MVP		0.49
MPC		2.3
ClinPred		0.89	D
GERP RS		4.8
Varity_R		0.75
gMVP		0.75

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: rs1830950664; hg19: chr9-137998640;