9-105464276-A-G

Position:

• chr9-105464276-A-G

Variant summary

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

The NM_001145313.3(FSD1L):​c.152A>G​(p.Asn51Ser) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: FSD1L NM_001145313.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.43

Genes affected

FSD1L (HGNC:13753): (fibronectin type III and SPRY domain containing 1 like) Predicted to be located in cytoplasm. Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

FSD1L (HGNC:):

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=0.21571884).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FSD1L	NM_001145313.3	c.152A>G	p.Asn51Ser	missense_variant	3/14	ENST00000481272.6	NP_001138785.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FSD1L	ENST00000481272.6	c.152A>G	p.Asn51Ser	missense_variant	3/14	2	NM_001145313.3	ENSP00000417492.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 24

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jul 20, 2022

The c.152A>G (p.N51S) alteration is located in exon 3 (coding exon 3) of the FSD1L gene. This alteration results from a A to G substitution at nucleotide position 152, causing the asparagine (N) at amino acid position 51 to be replaced by a serine (S). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.32
BayesDel_addAF	Benign	-0.21	T
BayesDel_noAF	Benign	-0.54
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.092	.;.;.;T;T;T
Eigen	Benign	0.057
Eigen_PC	Benign	0.12
FATHMM_MKL	Uncertain	0.91	D
LIST_S2	Uncertain	0.89	D;D;D;D;D;D
M_CAP	Benign	0.020	T
MetaRNN	Benign	0.22	T;T;T;T;T;T
MetaSVM	Benign	-0.86	T
MutationAssessor	Uncertain	2.3	.;.;.;M;.;.
PrimateAI	Uncertain	0.75	T
PROVEAN	Uncertain	-3.4	D;D;.;D;D;D
REVEL	Benign	0.15
Sift	Benign	0.053	T;D;.;D;D;D
Sift4G	Uncertain	0.017	D;D;T;D;D;D
Polyphen		0.037, 0.97, 0.0070	.;.;B;D;.;B
Vest4		0.21
MutPred		0.63		Loss of ubiquitination at K50 (P = 0.0742);.;.;Loss of ubiquitination at K50 (P = 0.0742);.;.;
MVP		0.34
ClinPred		0.92	D
GERP RS		3.9
Varity_R		0.19
gMVP		0.36

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: rs1297939565; hg19: chr9-108226557;