Variant 9-105539267-A-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001145313.3(FSD1L):c.1383A>T(p.Gln461His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000622 in 1,285,154 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000062 ( 0 hom. )

Consequence

FSD1L
NM_001145313.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.146

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 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=0.17974985).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FSD1L	NM_001145313.3 linkuse as main transcript	c.1383A>T	p.Gln461His	missense_variant	13/14	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.1383A>T	p.Gln461His	missense_variant	13/14	2	NM_001145313.3	ENSP00000417492.1	Q9BXM9-1
FSD1L	ENST00000374707.1 linkuse as main transcript	c.726A>T	p.Gln242His	missense_variant	7/8	1		ENSP00000363839.1	Q8N450
FSD1L	ENST00000394926.7 linkuse as main transcript	c.1320A>T	p.Gln440His	missense_variant	13/14	5		ENSP00000378384.3	F8W946
FSD1L	ENST00000484973.5 linkuse as main transcript	c.1284A>T	p.Gln428His	missense_variant	12/13	2		ENSP00000419691.1	A0A0C4DG97

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000397

AC:

AN:

125860

Hom.:

AF XY:

0.0000742

AC XY:

AN XY:

67372

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:

0.000293

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000622

AC:

AN:

1285154

Hom.:

Cov.:

AF XY:

0.0000125

AC XY:

AN XY:

638164

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:

0.000113

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ExAC

AF:

0.0000832

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

Oct 17, 2024

The c.1383A>T (p.Q461H) alteration is located in exon 13 (coding exon 13) of the FSD1L gene. This alteration results from a A to T substitution at nucleotide position 1383, causing the glutamine (Q) at amino acid position 461 to be replaced by a histidine (H). 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

0.17

BayesDel_addAF

Benign

-0.29

BayesDel_noAF

Benign

-0.36

CADD

Benign

DANN

Benign

0.97

DEOGEN2

Benign

0.022

.;T;T;T;T

Eigen

Benign

-0.43

Eigen_PC

Benign

-0.49

FATHMM_MKL

Benign

0.69

LIST_S2

Benign

0.77

T;T;T;T;T

M_CAP

Benign

0.068

MetaRNN

Benign

0.18

T;T;T;T;T

MetaSVM

Benign

-0.72

MutationAssessor

Benign

1.4

.;L;.;.;.

PrimateAI

Uncertain

0.64

PROVEAN

Benign

-1.4

N;N;N;N;N

REVEL

Uncertain

0.32

Sift

Benign

0.16

T;T;T;T;T

Sift4G

Benign

0.59

T;T;T;T;T

Polyphen

0.98, 0.99

.;D;.;D;.

Vest4

0.29

MutPred

0.52

.;Loss of sheet (P = 0.1158);.;.;.;

MVP

0.18

ClinPred

0.32

GERP RS

-6.1

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.059

gMVP

0.48

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