Variant chr9-105471926-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_001145313.3(FSD1L):c.362A>G(p.Asn121Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0397 in 1,378,182 control chromosomes in the GnomAD database, including 1,301 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.032 ( 137 hom., cov: 31)

Exomes 𝑓: 0.041 ( 1164 hom. )

Consequence

FSD1L
NM_001145313.3 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 1.86

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 Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0021950006).

BP6

Variant 9-105471926-A-G is Benign according to our data. Variant chr9-105471926-A-G is described in ClinVar as [Benign]. Clinvar id is 1267074.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0321 (4808/149984) while in subpopulation NFE AF= 0.0467 (3154/67544). AF 95% confidence interval is 0.0453. There are 137 homozygotes in gnomad4. There are 2326 alleles in male gnomad4 subpopulation. Median coverage is 31. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 137 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FSD1L	NM_001145313.3 linkuse as main transcript	c.362A>G	p.Asn121Ser	missense_variant	5/14	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.362A>G	p.Asn121Ser	missense_variant	5/14	2	NM_001145313.3	ENSP00000417492.1		Q9BXM9-1

Frequencies

GnomAD3 genomes

AF:

0.0321

AC:

4811

AN:

149886

Hom.:

137

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00792

Gnomad AMI

AF:

0.0617

Gnomad AMR

AF:

0.0256

Gnomad ASJ

AF:

0.0217

Gnomad EAS

AF:

0.000194

Gnomad SAS

AF:

0.00923

Gnomad FIN

AF:

0.0734

Gnomad MID

AF:

0.0191

Gnomad NFE

AF:

0.0467

Gnomad OTH

AF:

0.0282

GnomAD3 exomes

AF:

0.0427

AC:

3023

AN:

70834

Hom.:

AF XY:

0.0412

AC XY:

1611

AN XY:

39140

show subpopulations

Gnomad AFR exome

AF:

0.00835

Gnomad AMR exome

AF:

0.0198

Gnomad ASJ exome

AF:

0.0179

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0101

Gnomad FIN exome

AF:

0.0793

Gnomad NFE exome

AF:

0.0459

Gnomad OTH exome

AF:

0.0347

GnomAD4 exome

AF:

0.0407

AC:

49936

AN:

1228198

Hom.:

1164

Cov.:

AF XY:

0.0403

AC XY:

24342

AN XY:

603904

show subpopulations

Gnomad4 AFR exome

AF:

0.00563

Gnomad4 AMR exome

AF:

0.0230

Gnomad4 ASJ exome

AF:

0.0200

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00836

Gnomad4 FIN exome

AF:

0.0726

Gnomad4 NFE exome

AF:

0.0440

Gnomad4 OTH exome

AF:

0.0330

GnomAD4 genome

AF:

0.0321

AC:

4808

AN:

149984

Hom.:

137

Cov.:

AF XY:

0.0318

AC XY:

2326

AN XY:

73194

show subpopulations

Gnomad4 AFR

AF:

0.00790

Gnomad4 AMR

AF:

0.0255

Gnomad4 ASJ

AF:

0.0217

Gnomad4 EAS

AF:

0.000194

Gnomad4 SAS

AF:

0.00904

Gnomad4 FIN

AF:

0.0734

Gnomad4 NFE

AF:

0.0467

Gnomad4 OTH

AF:

0.0279

Alfa

AF:

0.0398

Hom.:

Bravo

AF:

0.0290

TwinsUK

AF:

0.0520

AC:

193

ALSPAC

AF:

0.0496

AC:

191

ESP6500AA

AF:

0.00795

AC:

ESP6500EA

AF:

0.0416

AC:

132

ExAC

AF:

0.0247

AC:

579

Asia WGS

AF:

0.00551

AC:

AN:

3464

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Feb 27, 2019	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.062

BayesDel_addAF

Benign

-0.68

BayesDel_noAF

Benign

-0.70

CADD

Benign

DANN

Uncertain

0.98

DEOGEN2

Benign

0.0043

.;.;.;T;T;T

Eigen

Benign

-0.46

Eigen_PC

Benign

-0.27

FATHMM_MKL

Benign

0.64

LIST_S2

Benign

0.82

T;T;T;T;T;T

MetaRNN

Benign

0.0022

T;T;T;T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.39

.;.;.;N;.;.

PrimateAI

Uncertain

0.58

PROVEAN

Benign

-0.70

N;N;.;N;N;N

REVEL

Benign

0.074

Sift

Benign

0.34

T;T;.;T;T;T

Sift4G

Benign

0.55

T;T;T;T;T;T

Polyphen

0.062, 0.0010

.;.;B;B;.;B

Vest4

0.057

ClinPred

0.012

GERP RS

3.8

Varity_R

0.048

gMVP

0.077

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