chr9-135119716-G-T

Variant names:

• chr9-135119716-G-T
• NM_001282611.2:c.996G>T

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001282611.2(OLFM1):​c.996G>T​(p.Lys332Asn) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: OLFM1 NM_001282611.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.82
• 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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.36153167).

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.996G>T	p.Lys332Asn	missense	Exon 6 of 6	NP_001269540.1	Q99784-1
	OLFM1	NM_001282612.1		c.915G>T	p.Lys305Asn	missense	Exon 6 of 6	NP_001269541.1	Q99784-5
	OLFM1	NM_014279.7		c.912G>T	p.Lys304Asn	missense	Exon 6 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.996G>T	p.Lys332Asn	missense	Exon 6 of 6	ENSP00000360858.3	Q99784-1
	OLFM1	ENST00000252854.8	TSL:1	c.942G>T	p.Lys314Asn	missense	Exon 6 of 6	ENSP00000252854.4	Q99784-3
	OLFM1	ENST00000483042.1	TSL:1	n.1429G>T		non_coding_transcript_exon	Exon 2 of 2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 33

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	Pathogenic	0.62
BayesDel_addAF	Uncertain	0.067	T
BayesDel_noAF	Benign	-0.14
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.61	D
Eigen	Uncertain	0.27
Eigen_PC	Uncertain	0.40
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Benign	0.83	T
M_CAP	Uncertain	0.14	D
MetaRNN	Benign	0.36	T
MetaSVM	Uncertain	0.45	D
MutationAssessor	Benign	0.97	L
PhyloP100		7.8
PrimateAI	Pathogenic	0.81	D
PROVEAN	Benign	-0.92	N
REVEL	Uncertain	0.48
Sift	Benign	0.065	T
Sift4G	Benign	0.50	T
Polyphen		0.97	D
Vest4		0.54
MutPred		0.57		Loss of ubiquitination at K332 (P = 0.0309)
MVP		0.24
MPC		2.3
ClinPred		0.79	D
GERP RS		5.1
Varity_R		0.48
gMVP		0.63
Mutation Taster		=36/64	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

hg19: chr9-138011562;