rs376946259

Variant names:

• chr11-7509875-C-G
• rs376946259
• NM_198474.4:c.896C>G

Your query was ambiguous. Multiple possible variants found:

• chr11-7509875-C-G
• chr11-7509875-C-T

Variant summary

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

The NM_198474.4(OLFML1):​c.896C>G​(p.Pro299Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000248 in 1,614,100 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P299L) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.000013 (0 hom., cov: 33)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: OLFML1 NM_198474.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.746
• Publications: 0 publications found

Genes affected

OLFML1 (HGNC:24473): (olfactomedin like 1) Predicted to be located in extracellular region. [provided by Alliance of Genome Resources, Apr 2022]

LOC124902806 (HGNC:):

SYT9-AS1 (HGNC:56173): (SYT9 antisense RNA 1)

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_198474.4. 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
	OLFML1	NM_198474.4	MANE Select	c.896C>G	p.Pro299Arg	missense	Exon 3 of 3	NP_940876.2	Q6UWY5
	OLFML1	NM_001370498.1		c.896C>G	p.Pro299Arg	missense	Exon 4 of 4	NP_001357427.1	Q6UWY5
	OLFML1	NM_001370499.1		c.488C>G	p.Pro163Arg	missense	Exon 3 of 3	NP_001357428.1	B4DN61

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OLFML1	ENST00000329293.4	TSL:1 MANE Select	c.896C>G	p.Pro299Arg	missense	Exon 3 of 3	ENSP00000332511.3	Q6UWY5
	OLFML1	ENST00000870572.1		c.926C>G	p.Pro309Arg	missense	Exon 3 of 3	ENSP00000540631.1
	OLFML1	ENST00000530135.5	TSL:2	c.896C>G	p.Pro299Arg	missense	Exon 4 of 4	ENSP00000433455.1	Q6UWY5

Frequencies

GnomAD3 genomes AF: 0.0000131 AC: 2 AN: 152210 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.0000241

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1461890 Hom.: 0 Cov.: 32 AF XY: 0.00000275 AC XY: 2 AN XY: 727248

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53420

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.00000180 AC: 2 AN: 1112010

Other (OTH) AF: 0.00 AC: 0 AN: 60396

GnomAD4 genome AF: 0.0000131 AC: 2 AN: 152210 Hom.: 0 Cov.: 33 AF XY: 0.0000269 AC XY: 2 AN XY: 74348

African (AFR) AF: 0.0000241 AC: 1 AN: 41450

American (AMR) AF: 0.00 AC: 0 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5200

South Asian (SAS) AF: 0.00 AC: 0 AN: 4830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10622

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 68038

Other (OTH) AF: 0.00 AC: 0 AN: 2088

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

EpiCase AF: 0.0000545

EpiControl AF: 0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.18
BayesDel_addAF	Uncertain	0.079	D
BayesDel_noAF	Benign	-0.12
CADD	Benign	18
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.56	D
Eigen	Benign	0.063
Eigen_PC	Benign	0.048
FATHMM_MKL	Benign	0.52	D
LIST_S2	Benign	0.69	T
M_CAP	Benign	0.082	D
MetaRNN	Uncertain	0.68	D
MetaSVM	Uncertain	0.40	D
MutationAssessor	Uncertain	2.1	M
PhyloP100		0.75
PrimateAI	Benign	0.38	T
PROVEAN	Pathogenic	-5.5	D
REVEL	Uncertain	0.49
Sift	Benign	0.044	D
Sift4G	Benign	0.10	T
Polyphen		0.58	P
Vest4		0.30
MutPred		0.69		Loss of ubiquitination at K296 (P = 0.0536)
MVP		0.84
MPC		0.15
ClinPred		0.90	D
GERP RS		5.5
Varity_R		0.31
gMVP		0.64
Mutation Taster		=88/12	polymorphism

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: rs376946259; hg19: chr11-7531106;