NM_198474.4:c.863C>G

Variant names:

• chr11-7509842-C-G
• rs1386720901
• NM_198474.4:c.863C>G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_198474.4(OLFML1):​c.863C>G​(p.Thr288Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,884 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 17/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: OLFML1 NM_198474.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.132
• 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.03284076).

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.863C>G	p.Thr288Ser	missense	Exon 3 of 3	NP_940876.2	Q6UWY5
	OLFML1	NM_001370498.1		c.863C>G	p.Thr288Ser	missense	Exon 4 of 4	NP_001357427.1	Q6UWY5
	OLFML1	NM_001370499.1		c.455C>G	p.Thr152Ser	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.863C>G	p.Thr288Ser	missense	Exon 3 of 3	ENSP00000332511.3	Q6UWY5
	OLFML1	ENST00000870572.1		c.893C>G	p.Thr298Ser	missense	Exon 3 of 3	ENSP00000540631.1
	OLFML1	ENST00000530135.5	TSL:2	c.863C>G	p.Thr288Ser	missense	Exon 4 of 4	ENSP00000433455.1	Q6UWY5

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD2 exomes AF: 0.00000398 AC: 1 AN: 251406 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000289

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461884 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 727240

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

American (AMR) AF: 0.0000224 AC: 1 AN: 44724

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: 0.00 AC: 0 AN: 1112002

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

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000756

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	Benign	0.064
BayesDel_addAF	Benign	-0.26	T
BayesDel_noAF	Benign	-0.53
CADD	Benign	8.4
DANN	Benign	0.67
DEOGEN2	Benign	0.10	T
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.072	N
LIST_S2	Benign	0.40	T
M_CAP	Benign	0.028	D
MetaRNN	Benign	0.033	T
MetaSVM	Benign	-0.84	T
MutationAssessor	Benign	-0.34	N
PhyloP100		0.13
PrimateAI	Benign	0.32	T
PROVEAN	Benign	0.58	N
REVEL	Benign	0.063
Sift	Benign	0.87	T
Sift4G	Benign	0.92	T
Polyphen		0.0020	B
Vest4		0.056
MutPred		0.42		Gain of disorder (P = 0.0438)
MVP		0.20
MPC		0.020
ClinPred		0.054	T
GERP RS		0.040
Varity_R		0.054
gMVP		0.36
Mutation Taster		=92/8	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: rs1386720901; hg19: chr11-7531073;