chr9-105534551-G-A

Position:

• chr9-105534551-G-A

Variant summary

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

The NM_001145313.3(FSD1L):​c.1084G>A​(p.Gly362Ser) 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: 5.37

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]

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=0.19307715).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FSD1L	NM_001145313.3	c.1084G>A	p.Gly362Ser	missense_variant	11/14	ENST00000481272.6	NP_001138785.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FSD1L	ENST00000481272.6	c.1084G>A	p.Gly362Ser	missense_variant	11/14	2	NM_001145313.3	ENSP00000417492.1
FSD1L	ENST00000374707.1	c.427G>A	p.Gly143Ser	missense_variant	5/8	1		ENSP00000363839.1
FSD1L	ENST00000394926.7	c.1021G>A	p.Gly341Ser	missense_variant	11/14	5		ENSP00000378384.3
FSD1L	ENST00000484973.5	c.985G>A	p.Gly329Ser	missense_variant	10/13	2		ENSP00000419691.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 28

GnomAD4 genome Cov.: 32

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

Mar 13, 2023

The c.1084G>A (p.G362S) alteration is located in exon 11 (coding exon 11) of the FSD1L gene. This alteration results from a G to A substitution at nucleotide position 1084, causing the glycine (G) at amino acid position 362 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	0.13
BayesDel_addAF	Benign	-0.11	T
BayesDel_noAF	Benign	-0.39
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.022	.;T;T;T;T
Eigen	Uncertain	0.48
Eigen_PC	Uncertain	0.55
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Uncertain	0.93	D;D;D;D;D
M_CAP	Benign	0.0070	T
MetaRNN	Benign	0.19	T;T;T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.6	.;L;.;.;.
PrimateAI	Uncertain	0.56	T
PROVEAN	Benign	-1.4	.;N;N;N;N
REVEL	Benign	0.088
Sift	Uncertain	0.028	.;D;D;D;T
Sift4G	Benign	0.25	T;T;T;T;T
Polyphen		0.97, 0.98	.;D;.;D;.
Vest4		0.19
MutPred		0.25		.;Gain of phosphorylation at G362 (P = 0.0137);.;.;.;
MVP		0.10
ClinPred		0.85	D
GERP RS		5.5
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.30
gMVP		0.46

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr9-108296832;