NM_001145313.3:c.778A>C

Variant names:

• chr9-105506590-A-C
• rs1188022977
• NM_001145313.3:c.778A>C

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.778A>C​(p.Thr260Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000259 in 1,541,438 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. T260A) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.0000066 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0000022 (0 hom.)
• Consequence: FSD1L NM_001145313.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.79
• Publications: 1 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: 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=0.20698091).

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.778A>C	p.Thr260Pro	missense	Exon 8 of 14	NP_001138785.1	Q9BXM9-1
	FSD1L	NM_001330739.2		c.682A>C	p.Thr228Pro	missense	Exon 7 of 14	NP_001317668.1	F8W946
	FSD1L	NM_001287191.2		c.682A>C	p.Thr228Pro	missense	Exon 7 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.778A>C	p.Thr260Pro	missense	Exon 8 of 14	ENSP00000417492.1	Q9BXM9-1
	FSD1L	ENST00000495708.5	TSL:1	c.778A>C	p.Thr260Pro	missense	Exon 8 of 11	ENSP00000420624.1	C9JD05
	FSD1L	ENST00000374707.1	TSL:1	c.121A>C	p.Thr41Pro	missense	Exon 2 of 8	ENSP00000363839.1	Q8N450

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152154 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000654

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.00000216 AC: 3 AN: 1389284 Hom.: 0 Cov.: 29 AF XY: 0.00000437 AC XY: 3 AN XY: 685922

African (AFR) AF: 0.00 AC: 0 AN: 31382

American (AMR) AF: 0.00 AC: 0 AN: 35688

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25090

East Asian (EAS) AF: 0.00 AC: 0 AN: 35628

South Asian (SAS) AF: 0.00 AC: 0 AN: 78978

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 49218

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5672

European-Non Finnish (NFE) AF: 0.00000280 AC: 3 AN: 1069994

Other (OTH) AF: 0.00 AC: 0 AN: 57634

GnomAD4 genome AF: 0.00000657 AC: 1 AN: 152154 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 74330

African (AFR) AF: 0.00 AC: 0 AN: 41420

American (AMR) AF: 0.0000654 AC: 1 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5206

South Asian (SAS) AF: 0.00 AC: 0 AN: 4820

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10614

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68026

Other (OTH) AF: 0.00 AC: 0 AN: 2092

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.099
BayesDel_addAF	Uncertain	0.11	D
BayesDel_noAF	Uncertain	-0.080
CADD	Benign	21
DANN	Uncertain	0.98
DEOGEN2	Benign	0.11	T
Eigen	Benign	-0.022
Eigen_PC	Benign	0.013
FATHMM_MKL	Uncertain	0.86	D
LIST_S2	Uncertain	0.91	D
M_CAP	Benign	0.035	D
MetaRNN	Benign	0.21	T
MetaSVM	Benign	-0.69	T
MutationAssessor	Uncertain	2.7	M
PhyloP100		2.8
PrimateAI	Uncertain	0.61	T
PROVEAN	Uncertain	-2.5	D
REVEL	Uncertain	0.35
Sift	Benign	0.062	T
Sift4G	Uncertain	0.031	D
Polyphen		0.71	P
Vest4		0.48
MutPred		0.56		Loss of ubiquitination at K258 (P = 0.0755)
MVP		0.20
ClinPred		0.93	D
GERP RS		1.6
Varity_R		0.23
gMVP		0.62
Mutation Taster		=41/59	disease causing

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: rs1188022977; hg19: chr9-108268871;