NM_001145313.3:c.1383A>T

Variant names:

• chr9-105539267-A-T
• rs773300554
• NM_001145313.3:c.1383A>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_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. 13/22 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: 0.0000062 (0 hom.)
• Consequence: FSD1L NM_001145313.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.146
• Publications: 0 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]

FKTN-AS1 (HGNC:55797): (FKTN antisense RNA 1)

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.17974985).

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.1383A>T	p.Gln461His	missense	Exon 13 of 14	NP_001138785.1	Q9BXM9-1
	FSD1L	NM_001330739.2		c.1320A>T	p.Gln440His	missense	Exon 13 of 14	NP_001317668.1	F8W946
	FSD1L	NM_001287191.2		c.1317A>T	p.Gln439His	missense	Exon 13 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.1383A>T	p.Gln461His	missense	Exon 13 of 14	ENSP00000417492.1	Q9BXM9-1
	FSD1L	ENST00000374707.1	TSL:1	c.726A>T	p.Gln242His	missense	Exon 7 of 8	ENSP00000363839.1	Q8N450
	FSD1L	ENST00000955870.1		c.1416A>T	p.Gln472His	missense	Exon 14 of 15	ENSP00000625929.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.0000397 AC: 5 AN: 125860 AF XY: 0.0000742

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 FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000622 AC: 8 AN: 1285154 Hom.: 0 Cov.: 20 AF XY: 0.0000125 AC XY: 8 AN XY: 638164

African (AFR) AF: 0.00 AC: 0 AN: 27684

American (AMR) AF: 0.00 AC: 0 AN: 25516

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 23518

East Asian (EAS) AF: 0.00 AC: 0 AN: 34608

South Asian (SAS) AF: 0.000113 AC: 8 AN: 70936

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 46106

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4992

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 997812

Other (OTH) AF: 0.00 AC: 0 AN: 53982

GnomAD4 genome Cov.: 32

ExAC AF: 0.0000832 AC: 2

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.17
BayesDel_addAF	Benign	-0.29	T
BayesDel_noAF	Benign	-0.36
CADD	Benign	17
DANN	Benign	0.97
DEOGEN2	Benign	0.022	T
Eigen	Benign	-0.43
Eigen_PC	Benign	-0.49
FATHMM_MKL	Benign	0.69	D
LIST_S2	Benign	0.77	T
M_CAP	Benign	0.068	D
MetaRNN	Benign	0.18	T
MetaSVM	Benign	-0.72	T
MutationAssessor	Benign	1.4	L
PhyloP100		0.15
PrimateAI	Uncertain	0.64	T
PROVEAN	Benign	-1.4	N
REVEL	Uncertain	0.32
Sift	Benign	0.16	T
Sift4G	Benign	0.59	T
Polyphen		0.98	D
Vest4		0.29
MutPred		0.52		Loss of sheet (P = 0.1158)
MVP		0.18
ClinPred		0.32	T
GERP RS		-6.1
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.059
gMVP		0.48
Mutation Taster		=79/21	polymorphism

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: rs773300554; hg19: chr9-108301548;