9-105472013-A-G

Position:

• chr9-105472013-A-G

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_031919.5(FSD1L):​c.353A>G​(p.Lys118Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0557 in 1,424,492 control chromosomes in the GnomAD database, including 2,485 homozygotes. In-silico tool predicts a benign outcome for this variant. 9/11 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.043 (209 hom., cov: 32)
  • Exomes 𝑓: 0.057 (2276 hom.)
• Consequence: FSD1L NM_031919.5 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 1.65

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0027226806).
• BP6: Variant 9-105472013-A-G is Benign according to our data. Variant chr9-105472013-A-G is described in ClinVar as [Benign]. Clinvar id is 1248102.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0634 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FSD1L	NM_001145313.3	c.441+8A>G		splice_region_variant, intron_variant		ENST00000481272.6	NP_001138785.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FSD1L	ENST00000481272.6	c.441+8A>G		splice_region_variant, intron_variant		2	NM_001145313.3	ENSP00000417492.1

Frequencies

GnomAD3 genomes AF: 0.0432 AC: 6567 AN: 151980 Hom.: 210 Cov.: 32

Gnomad AFR AF: 0.0124

Gnomad AMI AF: 0.0921

Gnomad AMR AF: 0.0467

Gnomad ASJ AF: 0.0608

Gnomad EAS AF: 0.000192

Gnomad SAS AF: 0.0182

Gnomad FIN AF: 0.0377

Gnomad MID AF: 0.0828

Gnomad NFE AF: 0.0650

Gnomad OTH AF: 0.0560

GnomAD3 exomes AF: 0.0463 AC: 3552 AN: 76700 Hom.: 116 AF XY: 0.0451 AC XY: 1896 AN XY: 42042

Gnomad AFR exome AF: 0.00863

Gnomad AMR exome AF: 0.0337

Gnomad ASJ exome AF: 0.0540

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0204

Gnomad FIN exome AF: 0.0408

Gnomad NFE exome AF: 0.0634

Gnomad OTH exome AF: 0.0514

GnomAD4 exome AF: 0.0572 AC: 72736 AN: 1272396 Hom.: 2276 Cov.: 23 AF XY: 0.0567 AC XY: 35531 AN XY: 626606

Gnomad4 AFR exome AF: 0.00849

Gnomad4 AMR exome AF: 0.0416

Gnomad4 ASJ exome AF: 0.0615

Gnomad4 EAS exome AF: 0.000104

Gnomad4 SAS exome AF: 0.0195

Gnomad4 FIN exome AF: 0.0422

Gnomad4 NFE exome AF: 0.0630

Gnomad4 OTH exome AF: 0.0547

GnomAD4 genome AF: 0.0431 AC: 6560 AN: 152096 Hom.: 209 Cov.: 32 AF XY: 0.0413 AC XY: 3070 AN XY: 74374

Gnomad4 AFR AF: 0.0123

Gnomad4 AMR AF: 0.0466

Gnomad4 ASJ AF: 0.0608

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.0185

Gnomad4 FIN AF: 0.0377

Gnomad4 NFE AF: 0.0650

Gnomad4 OTH AF: 0.0555

Alfa AF: 0.0610 Hom.: 463

Bravo AF: 0.0450

ESP6500AA AF: 0.0101 AC: 14

ESP6500EA AF: 0.0605 AC: 192

ExAC AF: 0.0367 AC: 895

Asia WGS AF: 0.0130 AC: 46 AN: 3474

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

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

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Benign	-0.71	T
BayesDel_noAF	Benign	-0.74
CADD	Benign	3.2
DANN	Benign	0.91
Eigen	Benign	-0.36
Eigen_PC	Benign	-0.56
FATHMM_MKL	Benign	0.055	N
LIST_S2	Benign	0.26	T
MetaRNN	Benign	0.0027	T
MetaSVM	Benign	-1.1	T
Sift4G	Benign	0.13	T
Polyphen		0.0040	B
Vest4		0.043
ClinPred		0.0025	T
GERP RS		2.3

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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

Other links and lift over

dbSNP: rs34998811; hg19: chr9-108234294; COSMIC: COSV66005068;