Variant chr9-105546475-A-C 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.1585A>C(p.Thr529Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000717 in 1,393,988 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 7.2e-7 ( 0 hom. )

Consequence

FSD1L
NM_001145313.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.131

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:

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=0.051348448).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FSD1L	NM_001145313.3 linkuse as main transcript	c.1585A>C	p.Thr529Pro	missense_variant	14/14	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.1585A>C	p.Thr529Pro	missense_variant	14/14	2	NM_001145313.3	ENSP00000417492.1	Q9BXM9-1
FSD1L	ENST00000374707.1 linkuse as main transcript	c.928A>C	p.Thr310Pro	missense_variant	8/8	1		ENSP00000363839.1	Q8N450
FSD1L	ENST00000394926.7 linkuse as main transcript	c.1522A>C	p.Thr508Pro	missense_variant	14/14	5		ENSP00000378384.3	F8W946
FSD1L	ENST00000484973.5 linkuse as main transcript	c.1486A>C	p.Thr496Pro	missense_variant	13/13	2		ENSP00000419691.1	A0A0C4DG97

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000654

AC:

AN:

152894

Hom.:

AF XY:

0.0000124

AC XY:

AN XY:

80482

show subpopulations

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:

0.0000468

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

7.17e-7

AC:

AN:

1393988

Hom.:

Cov.:

AF XY:

0.00000145

AC XY:

AN XY:

687330

show subpopulations

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:

0.0000128

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

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 14, 2021

The c.1585A>C (p.T529P) alteration is located in exon 14 (coding exon 14) of the FSD1L gene. This alteration results from a A to C substitution at nucleotide position 1585, causing the threonine (T) at amino acid position 529 to be replaced by a proline (P). 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

0.059

BayesDel_addAF

Benign

-0.24

BayesDel_noAF

Benign

-0.45

CADD

Benign

DANN

Benign

0.91

DEOGEN2

Benign

0.0062

.;T;T;T;T

Eigen

Benign

-1.1

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.47

LIST_S2

Benign

0.53

T;T;T;T;T

M_CAP

Benign

0.022

MetaRNN

Benign

0.051

T;T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

-0.69

.;N;.;.;.

PrimateAI

Benign

0.45

PROVEAN

Benign

0.20

.;N;N;N;N

REVEL

Benign

0.14

Sift

Pathogenic

0.0

.;D;D;D;D

Sift4G

Pathogenic

0.0

D;.;D;D;.

Polyphen

0.0

.;B;.;B;.

Vest4

0.14

MutPred

0.22

.;Gain of sheet (P = 0.0125);.;.;.;

MVP

0.099

ClinPred

0.040

GERP RS

-5.0

Varity_R

0.12

gMVP

0.43

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