11-7509560-C-A

Variant names:

• chr11-7509560-C-A
• rs143220829
• NM_198474.4:c.581C>A

Variant summary

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

The NM_198474.4(OLFML1):​c.581C>A​(p.Ala194Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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. A194V) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 33)
• Consequence: OLFML1 NM_198474.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.74
• 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.581C>A	p.Ala194Glu	missense	Exon 3 of 3	NP_940876.2	Q6UWY5
	OLFML1	NM_001370498.1		c.581C>A	p.Ala194Glu	missense	Exon 4 of 4	NP_001357427.1	Q6UWY5
	OLFML1	NM_001370499.1		c.173C>A	p.Ala58Glu	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.581C>A	p.Ala194Glu	missense	Exon 3 of 3	ENSP00000332511.3	Q6UWY5
	OLFML1	ENST00000870572.1		c.611C>A	p.Ala204Glu	missense	Exon 3 of 3	ENSP00000540631.1
	OLFML1	ENST00000530135.5	TSL:2	c.581C>A	p.Ala194Glu	missense	Exon 4 of 4	ENSP00000433455.1	Q6UWY5

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.22
BayesDel_addAF	Uncertain	0.15	D
BayesDel_noAF	Uncertain	-0.030
CADD	Uncertain	23
DANN	Benign	0.90
DEOGEN2	Benign	0.13	T
Eigen	Benign	0.12
Eigen_PC	Uncertain	0.23
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Benign	0.81	T
M_CAP	Benign	0.050	D
MetaRNN	Uncertain	0.46	T
MetaSVM	Uncertain	-0.12	T
MutationAssessor	Benign	1.2	L
PhyloP100		2.7
PrimateAI	Benign	0.38	T
PROVEAN	Benign	1.5	N
REVEL	Uncertain	0.46
Sift	Benign	1.0	T
Sift4G	Benign	0.54	T
Polyphen		0.82	P
Vest4		0.23
MutPred		0.66		Gain of disorder (P = 0.0429)
MVP		0.78
MPC		0.14
ClinPred		0.78	D
GERP RS		5.8
Varity_R		0.25
gMVP		0.59
Mutation Taster		=70/30	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: rs143220829; hg19: chr11-7530791;