chr9-135095927-G-T

Variant names:

• chr9-135095927-G-T
• rs1205344491
• NM_001282611.2:c.364G>T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001282611.2(OLFM1):​c.364G>T​(p.Val122Leu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000205 in 1,461,202 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: 30)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: OLFM1 NM_001282611.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.93

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

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.24245307).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
OLFM1	NM_001282611.2	c.364G>T	p.Val122Leu	missense_variant	Exon 3 of 6	ENST00000371793.8	NP_001269540.1
OLFM1	NM_014279.5	c.310G>T	p.Val104Leu	missense_variant	Exon 3 of 6		NP_055094.1
OLFM1	NM_001282612.1	c.283G>T	p.Val95Leu	missense_variant	Exon 3 of 6		NP_001269541.1
OLFM1	NM_006334.4	c.310G>T	p.Val104Leu	missense_variant	Exon 3 of 4		NP_006325.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
OLFM1	ENST00000371793.8	c.364G>T	p.Val122Leu	missense_variant	Exon 3 of 6	3	NM_001282611.2	ENSP00000360858.3

Frequencies

GnomAD3 genomes Cov.: 30

GnomAD3 exomes AF: 0.00000399 AC: 1 AN: 250934 Hom.: 0 AF XY: 0.00000737 AC XY: 1 AN XY: 135694

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 SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000882

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000205 AC: 3 AN: 1461202 Hom.: 0 Cov.: 33 AF XY: 0.00000138 AC XY: 1 AN XY: 726884

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 9.00e-7

Gnomad4 OTH exome AF: 0.0000331

GnomAD4 genome Cov.: 30

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.78
BayesDel_addAF	Benign	-0.037	T
BayesDel_noAF	Benign	-0.29
CADD	Uncertain	24
DANN	Uncertain	0.97
DEOGEN2	Benign	0.036	.;.;T;.;T;.;T;T
Eigen	Benign	0.13
Eigen_PC	Uncertain	0.26
FATHMM_MKL	Uncertain	0.91	D
LIST_S2	Uncertain	0.96	D;D;D;D;D;D;D;D
M_CAP	Benign	0.0083	T
MetaRNN	Benign	0.24	T;T;T;T;T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.8	.;.;.;.;.;L;L;.
PrimateAI	Uncertain	0.76	T
PROVEAN	Benign	-1.9	N;N;N;N;N;N;N;N
REVEL	Benign	0.12
Sift	Benign	0.10	T;T;T;T;T;T;T;T
Sift4G	Benign	0.072	T;T;T;T;T;D;T;T
Polyphen		0.85, 0.0090	.;.;.;.;.;P;B;.
Vest4		0.67
MutPred		0.40		.;.;.;.;.;Loss of MoRF binding (P = 0.0885);Loss of MoRF binding (P = 0.0885);.;
MVP		0.24
MPC		1.0
ClinPred		0.56	D
GERP RS		4.6
Varity_R		0.11
gMVP		0.77

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: rs1205344491; hg19: chr9-137987773;