Variant 9-105506415-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001145313.3(FSD1L):c.603G>T(p.Glu201Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000767 in 1,550,594 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00042 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000039 ( 0 hom. )

Consequence

FSD1L
NM_001145313.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.50

Variant links:

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 links:

FSD1L (HGNC:):

FSD1L links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.029954195).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FSD1L	NM_001145313.3 linkuse as main transcript	c.603G>T	p.Glu201Asp	missense_variant	8/14	ENST00000481272.6	NP_001138785.1	Q9BXM9-1Q8N450

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FSD1L	ENST00000481272.6 linkuse as main transcript	c.603G>T	p.Glu201Asp	missense_variant	8/14	2	NM_001145313.3	ENSP00000417492.1		Q9BXM9-1

Frequencies

GnomAD3 genomes

AF:

0.000422

AC:

AN:

151728

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00143

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000197

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.000962

GnomAD3 exomes

AF:

0.0000823

AC:

AN:

158036

Hom.:

AF XY:

0.0000480

AC XY:

AN XY:

83372

show subpopulations

Gnomad AFR exome

AF:

0.00110

Gnomad AMR exome

AF:

0.000121

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:

0.0000162

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000393

AC:

AN:

1398752

Hom.:

Cov.:

AF XY:

0.0000217

AC XY:

AN XY:

689904

show subpopulations

Gnomad4 AFR exome

AF:

0.00127

Gnomad4 AMR exome

AF:

0.000168

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:

0.00000185

Gnomad4 OTH exome

AF:

0.000120

GnomAD4 genome

AF:

0.000421

AC:

AN:

151842

Hom.:

Cov.:

AF XY:

0.000350

AC XY:

AN XY:

74198

show subpopulations

Gnomad4 AFR

AF:

0.00143

Gnomad4 AMR

AF:

0.000197

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.000953

Alfa

AF:

0.000285

Hom.:

Bravo

AF:

0.000457

ExAC

AF:

0.000120

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jul 19, 2023

The c.603G>T (p.E201D) alteration is located in exon 8 (coding exon 8) of the FSD1L gene. This alteration results from a G to T substitution at nucleotide position 603, causing the glutamic acid (E) at amino acid position 201 to be replaced by an aspartic acid (D). 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

0.27

BayesDel_addAF

Benign

-0.37

BayesDel_noAF

Benign

-0.35

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.016

.;.;T;T;T

Eigen

Benign

0.13

Eigen_PC

Benign

0.14

FATHMM_MKL

Uncertain

0.90

LIST_S2

Benign

0.79

T;T;T;T;T

M_CAP

Benign

0.016

MetaRNN

Benign

0.030

T;T;T;T;T

MetaSVM

Benign

-0.80

MutationAssessor

Uncertain

2.5

.;.;M;.;.

PrimateAI

Uncertain

0.70

PROVEAN

Benign

-1.2

N;N;N;N;N

REVEL

Benign

0.10

Sift

Benign

0.48

T;T;T;T;T

Sift4G

Uncertain

0.015

D;D;D;D;D

Polyphen

0.87, 0.76

.;.;P;.;P

Vest4

0.37

MutPred

0.39

Gain of ubiquitination at K198 (P = 0.1283);.;Gain of ubiquitination at K198 (P = 0.1283);.;.;

MVP

0.099

ClinPred

0.072

GERP RS

2.6

Varity_R

0.075

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over