9-105539295-C-T

Variant names:

• chr9-105539295-C-T
• NM_001145313.3:c.1411C>T

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PM2 PP5_Moderate

The NM_001145313.3(FSD1L):​c.1411C>T​(p.Gln471*) variant causes a stop gained change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Pathogenic (★). Variant results in nonsense mediated mRNA decay.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: FSD1L NM_001145313.3 stop_gained
• Clinical Significance: Pathogenic criteria provided, single submitter P:1
• Conservation: PhyloP100: 4.66
• 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 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP5: Variant 9-105539295-C-T is Pathogenic according to our data. Variant chr9-105539295-C-T is described in ClinVar as Pathogenic. ClinVar VariationId is 2628091.Status of the report is criteria_provided_single_submitter, 1 stars.

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.1411C>T	p.Gln471*	stop_gained	Exon 13 of 14	NP_001138785.1	Q9BXM9-1
	FSD1L	NM_001330739.2		c.1348C>T	p.Gln450*	stop_gained	Exon 13 of 14	NP_001317668.1	F8W946
	FSD1L	NM_001287191.2		c.1345C>T	p.Gln449*	stop_gained	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.1411C>T	p.Gln471*	stop_gained	Exon 13 of 14	ENSP00000417492.1	Q9BXM9-1
	FSD1L	ENST00000374707.1	TSL:1	c.754C>T	p.Gln252*	stop_gained	Exon 7 of 8	ENSP00000363839.1	Q8N450
	FSD1L	ENST00000955870.1		c.1444C>T	p.Gln482*	stop_gained	Exon 14 of 15	ENSP00000625929.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1353668 Hom.: 0 Cov.: 24 AF XY: 0.00 AC XY: 0 AN XY: 669184

African (AFR) AF: 0.00 AC: 0 AN: 29666

American (AMR) AF: 0.00 AC: 0 AN: 29920

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24354

East Asian (EAS) AF: 0.00 AC: 0 AN: 35204

South Asian (SAS) AF: 0.00 AC: 0 AN: 74880

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 47604

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5318

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1050278

Other (OTH) AF: 0.00 AC: 0 AN: 56444

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Pathogenic

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
1	-	-	Hydrocephalus, nonsyndromic, autosomal recessive 1 (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Pathogenic	0.61	D
BayesDel_noAF	Pathogenic	0.63
CADD	Pathogenic	40
DANN	Uncertain	1.0
Eigen	Pathogenic	1.1
Eigen_PC	Pathogenic	0.93
FATHMM_MKL	Pathogenic	0.98	D
PhyloP100		4.7
Vest4		0.34
GERP RS		5.7
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Mutation Taster		=11/189	disease causing (fs/PTC)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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

hg19: chr9-108301576;