Variant chr9-105535122-T-A 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.1182T>A(p.Asp394Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000657 in 152,266 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)

Consequence

FSD1L
NM_001145313.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.158

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:

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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=0.0550552).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FSD1L	NM_001145313.3 linkuse as main transcript	c.1182T>A	p.Asp394Glu	missense_variant	12/14	ENST00000481272.6	NP_001138785.1	Q9BXM9-1Q8N450

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
FSD1L	ENST00000481272.6 linkuse as main transcript	c.1182T>A	p.Asp394Glu	missense_variant	12/14	2	NM_001145313.3	ENSP00000417492.1	Q9BXM9-1
FSD1L	ENST00000374707.1 linkuse as main transcript	c.525T>A	p.Asp175Glu	missense_variant	6/8	1		ENSP00000363839.1	Q8N450
FSD1L	ENST00000394926.7 linkuse as main transcript	c.1119T>A	p.Asp373Glu	missense_variant	12/14	5		ENSP00000378384.3	F8W946
FSD1L	ENST00000484973.5 linkuse as main transcript	c.1083T>A	p.Asp361Glu	missense_variant	11/13	2		ENSP00000419691.1	A0A0C4DG97

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152148

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

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:

0.000479

GnomAD4 exome

Cov.:

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152266

Hom.:

Cov.:

AF XY:

0.0000134

AC XY:

AN XY:

74458

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

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:

0.000474

Bravo

AF:

0.00000756

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

Jan 18, 2023

The c.1182T>A (p.D394E) alteration is located in exon 12 (coding exon 12) of the FSD1L gene. This alteration results from a T to A substitution at nucleotide position 1182, causing the aspartic acid (D) at amino acid position 394 to be replaced by a glutamic acid (E). 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

0.23

BayesDel_addAF

Benign

-0.26

BayesDel_noAF

Benign

-0.61

CADD

Benign

7.0

DANN

Benign

0.92

DEOGEN2

Benign

0.018

.;T;T;T;T

Eigen

Benign

-1.5

Eigen_PC

Benign

-1.5

FATHMM_MKL

Benign

0.45

LIST_S2

Benign

0.82

T;T;T;T;T

M_CAP

Benign

0.020

MetaRNN

Benign

0.055

T;T;T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.94

.;L;.;.;.

PrimateAI

Uncertain

0.71

PROVEAN

Benign

-1.2

.;N;N;N;N

REVEL

Benign

0.15

Sift

Benign

0.16

.;T;T;T;T

Sift4G

Benign

0.22

T;T;T;T;T

Polyphen

0.023, 0.027

.;B;.;B;.

Vest4

0.084

MutPred

0.39

.;Loss of sheet (P = 0.0457);.;.;.;

MVP

0.11

ClinPred

0.12

GERP RS

-9.8

Varity_R

0.18

gMVP

0.52

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