9-135095885-A-T

Variant names:

• chr9-135095885-A-T
• rs1368600876
• NM_001282611.2:c.322A>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001282611.2(OLFM1):​c.322A>T​(p.Ile108Leu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000753 in 1,461,104 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 30)
  • Exomes 𝑓: 0.0000075 (0 hom.)
• Consequence: OLFM1 NM_001282611.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 9.08
• 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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.22900623).

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.322A>T	p.Ile108Leu	missense	Exon 3 of 6	NP_001269540.1	Q99784-1
	OLFM1	NM_001282612.1		c.241A>T	p.Ile81Leu	missense	Exon 3 of 6	NP_001269541.1	Q99784-5
	OLFM1	NM_014279.7		c.238A>T	p.Ile80Leu	missense	Exon 3 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.322A>T	p.Ile108Leu	missense	Exon 3 of 6	ENSP00000360858.3	Q99784-1
	OLFM1	ENST00000252854.8	TSL:1	c.268A>T	p.Ile90Leu	missense	Exon 3 of 6	ENSP00000252854.4	Q99784-3
	OLFM1	ENST00000277415.15	TSL:1	c.268A>T	p.Ile90Leu	missense	Exon 3 of 4	ENSP00000277415.11	Q99784-4

Frequencies

GnomAD3 genomes Cov.: 30

GnomAD2 exomes AF: 0.00000798 AC: 2 AN: 250712 AF XY: 0.0000147

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000177

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000753 AC: 11 AN: 1461104 Hom.: 0 Cov.: 33 AF XY: 0.00000550 AC XY: 4 AN XY: 726836

African (AFR) AF: 0.00 AC: 0 AN: 33474

American (AMR) AF: 0.00 AC: 0 AN: 44686

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26082

East Asian (EAS) AF: 0.00 AC: 0 AN: 39698

South Asian (SAS) AF: 0.00 AC: 0 AN: 86254

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53232

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5762

European-Non Finnish (NFE) AF: 0.00000990 AC: 11 AN: 1111570

Other (OTH) AF: 0.00 AC: 0 AN: 60346

GnomAD4 genome Cov.: 30

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

EpiCase AF: 0.00

EpiControl AF: 0.0000595

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	0.44
BayesDel_addAF	Benign	-0.034	T
BayesDel_noAF	Benign	-0.27
CADD	Benign	22
DANN	Benign	0.94
DEOGEN2	Benign	0.027	T
Eigen	Benign	0.13
Eigen_PC	Uncertain	0.24
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Uncertain	0.90	D
M_CAP	Benign	0.015	T
MetaRNN	Benign	0.23	T
MetaSVM	Benign	-0.96	T
MutationAssessor	Benign	1.9	L
PhyloP100		9.1
PrimateAI	Uncertain	0.70	T
PROVEAN	Benign	-1.1	N
REVEL	Benign	0.25
Sift	Benign	0.038	D
Sift4G	Uncertain	0.024	D
Polyphen		0.97	D
Vest4		0.64
MutPred		0.41		Loss of catalytic residue at I108 (P = 0.0468)
MVP		0.16
MPC		1.1
ClinPred		0.41	T
GERP RS		4.7
PromoterAI		0.00020	Neutral
Varity_R		0.19
gMVP		0.58
Mutation Taster		=42/58	disease causing

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs1368600876; hg19: chr9-137987731; COSMIC: COSV52962767; COSMIC: COSV52962767;