9-105471926-A-G

Variant names:

• chr9-105471926-A-G
• rs28503319
• NM_001145313.3:c.362A>G

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

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. 13/21 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
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 1.86
• Publications: 8 publications found

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]

ACMG classification

Our verdict: Benign. The variant received -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 VariationId 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 the male GnomAd4 subpopulation. Median coverage is 31. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 137 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001145313.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FSD1L	NM_001145313.3	MANE Select	c.362A>G	p.Asn121Ser	missense	Exon 5 of 14	NP_001138785.1	Q9BXM9-1
	FSD1L	NM_001330739.2		c.266A>G	p.Asn89Ser	missense	Exon 4 of 14	NP_001317668.1	F8W946
	FSD1L	NM_001287191.2		c.266A>G	p.Asn89Ser	missense	Exon 4 of 14	NP_001274120.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FSD1L	ENST00000481272.6	TSL:2 MANE Select	c.362A>G	p.Asn121Ser	missense	Exon 5 of 14	ENSP00000417492.1	Q9BXM9-1
	FSD1L	ENST00000495708.5	TSL:1	c.362A>G	p.Asn121Ser	missense	Exon 5 of 11	ENSP00000420624.1	C9JD05
	FSD1L	ENST00000469022.5	TSL:1	c.266A>G	p.Asn89Ser	missense	Exon 4 of 4	ENSP00000487223.1	Q9BXM9-3

Frequencies

GnomAD3 genomes AF: 0.0321 AC: 4811 AN: 149886 Hom.: 137 Cov.: 31

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

GnomAD2 exomes AF: 0.0427 AC: 3023 AN: 70834 AF XY: 0.0412

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 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.: 21 AF XY: 0.0403 AC XY: 24342 AN XY: 603904

African (AFR) AF: 0.00563 AC: 134 AN: 23800

American (AMR) AF: 0.0230 AC: 257 AN: 11184

Ashkenazi Jewish (ASJ) AF: 0.0200 AC: 414 AN: 20670

East Asian (EAS) AF: 0.00 AC: 0 AN: 27728

South Asian (SAS) AF: 0.00836 AC: 438 AN: 52390

European-Finnish (FIN) AF: 0.0726 AC: 3371 AN: 46454

Middle Eastern (MID) AF: 0.0249 AC: 130 AN: 5216

European-Non Finnish (NFE) AF: 0.0440 AC: 43514 AN: 989860

Other (OTH) AF: 0.0330 AC: 1678 AN: 50896

GnomAD4 genome AF: 0.0321 AC: 4808 AN: 149984 Hom.: 137 Cov.: 31 AF XY: 0.0318 AC XY: 2326 AN XY: 73194

African (AFR) AF: 0.00790 AC: 325 AN: 41126

American (AMR) AF: 0.0255 AC: 384 AN: 15040

Ashkenazi Jewish (ASJ) AF: 0.0217 AC: 75 AN: 3464

East Asian (EAS) AF: 0.000194 AC: 1 AN: 5152

South Asian (SAS) AF: 0.00904 AC: 43 AN: 4758

European-Finnish (FIN) AF: 0.0734 AC: 707 AN: 9626

Middle Eastern (MID) AF: 0.0172 AC: 5 AN: 290

European-Non Finnish (NFE) AF: 0.0467 AC: 3154 AN: 67544

Other (OTH) AF: 0.0279 AC: 58 AN: 2076

Alfa AF: 0.0403 Hom.: 294

Bravo AF: 0.0290

TwinsUK AF: 0.0520 AC: 193

ALSPAC AF: 0.0496 AC: 191

ESP6500AA AF: 0.00795 AC: 11

ESP6500EA AF: 0.0416 AC: 132

ExAC AF: 0.0247 AC: 579

Asia WGS AF: 0.00551 AC: 20 AN: 3464

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.062
BayesDel_addAF	Benign	-0.68	T
BayesDel_noAF	Benign	-0.70
CADD	Benign	16
DANN	Uncertain	0.98
DEOGEN2	Benign	0.0043	T
Eigen	Benign	-0.46
Eigen_PC	Benign	-0.27
FATHMM_MKL	Benign	0.64	D
LIST_S2	Benign	0.82	T
MetaRNN	Benign	0.0022	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.39	N
PhyloP100		1.9
PrimateAI	Uncertain	0.58	T
PROVEAN	Benign	-0.70	N
REVEL	Benign	0.074
Sift	Benign	0.34	T
Sift4G	Benign	0.55	T
Polyphen		0.062	B
Vest4		0.057
ClinPred		0.012	T
GERP RS		3.8
Varity_R		0.048
gMVP		0.077
Mutation Taster		=87/13	polymorphism (auto)

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

Other links and lift over

dbSNP: rs28503319; hg19: chr9-108234207;