9-135106794-C-A

Variant names:

• chr9-135106794-C-A
• rs1830950664
• NM_001282611.2:c.722C>A

Variant summary

Our verdict is Uncertain significance. The variant received 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
• Publications: 0 publications found

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]

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001282611.2. 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
	OLFM1	NM_001282611.2	MANE Select	c.722C>A	p.Thr241Asn	missense	Exon 5 of 6	NP_001269540.1	Q99784-1
	OLFM1	NM_001282612.1		c.641C>A	p.Thr214Asn	missense	Exon 5 of 6	NP_001269541.1	Q99784-5
	OLFM1	NM_014279.7		c.638C>A	p.Thr213Asn	missense	Exon 5 of 6	NP_055094.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OLFM1	ENST00000371793.8	TSL:3 MANE Select	c.722C>A	p.Thr241Asn	missense	Exon 5 of 6	ENSP00000360858.3	Q99784-1
	OLFM1	ENST00000252854.8	TSL:1	c.668C>A	p.Thr223Asn	missense	Exon 5 of 6	ENSP00000252854.4	Q99784-3
	OLFM1	ENST00000483042.1	TSL:1	n.1155C>A		non_coding_transcript_exon	Exon 1 of 2

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 34

Alfa AF: 0.00 Hom.: 0

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	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
Eigen	Uncertain	0.66
Eigen_PC	Uncertain	0.63
FATHMM_MKL	Uncertain	0.97	D
LIST_S2	Uncertain	0.96	D
M_CAP	Uncertain	0.23	D
MetaRNN	Uncertain	0.57	D
MetaSVM	Uncertain	0.74	D
MutationAssessor	Uncertain	2.0	M
PhyloP100		6.0
PrimateAI	Pathogenic	0.83	D
PROVEAN	Benign	-0.91	N
REVEL	Uncertain	0.55
Sift	Uncertain	0.0020	D
Sift4G	Benign	0.078	T
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
Mutation Taster		=46/54	disease causing

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: rs1830950664; hg19: chr9-137998640;