chr11-7509905-A-G

Position:

• chr11-7509905-A-G

Variant summary

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

The NM_198474.4(OLFML1):​c.926A>G​(p.Asp309Gly) variant causes a missense change. The variant allele was found at a frequency of 0.000000684 in 1,461,888 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: Not reported in ClinVar
• Conservation: PhyloP100: 5.82

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

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
OLFML1	NM_198474.4	c.926A>G	p.Asp309Gly	missense_variant	3/3	ENST00000329293.4
LOC124902806	XM_047428005.1	c.*1088-1722T>C		intron_variant
OLFML1	NM_001370498.1	c.926A>G	p.Asp309Gly	missense_variant	4/4
OLFML1	NM_001370499.1	c.518A>G	p.Asp173Gly	missense_variant	3/3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
OLFML1	ENST00000329293.4	c.926A>G	p.Asp309Gly	missense_variant	3/3	1	NM_198474.4	P1
SYT9-AS1	ENST00000530201.2	n.1350+2218T>C		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD3 exomes AF: 0.00000796 AC: 2 AN: 251408 Hom.: 0 AF XY: 0.0000147 AC XY: 2 AN XY: 135904

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: 0.0000176

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461888 Hom.: 0 Cov.: 32 AF XY: 0.00000138 AC XY: 1 AN XY: 727246

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: 8.99e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ExAC AF: 0.0000165 AC: 2

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.23
BayesDel_addAF	Pathogenic	0.23	D
BayesDel_noAF	Uncertain	0.11
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.57	D;D
Eigen	Uncertain	0.38
Eigen_PC	Uncertain	0.42
FATHMM_MKL	Pathogenic	0.97	D
M_CAP	Uncertain	0.16	D
MetaRNN	Uncertain	0.63	D;D
MetaSVM	Uncertain	0.35	D
MutationAssessor	Uncertain	2.8	M;M
MutationTaster	Benign	0.95	D;D;D
PrimateAI	Uncertain	0.56	T
PROVEAN	Pathogenic	-5.2	D;D
REVEL	Pathogenic	0.71
Sift	Uncertain	0.0070	D;D
Sift4G	Uncertain	0.036	D;D
Polyphen		0.70	P;P
Vest4		0.63
MutPred		0.58		Loss of disorder (P = 0.1713);Loss of disorder (P = 0.1713);
MVP		0.83
MPC		0.079
ClinPred		0.98	D
GERP RS		3.1
Varity_R		0.90
gMVP		0.71

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: rs755256144; hg19: chr11-7531136;