19-4307901-C-G

Variant names:

• chr19-4307901-C-G
• rs149694101
• NM_024333.3:c.263C>G

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_024333.3(FSD1):​c.263C>G​(p.Thr88Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict 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. T88M) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: FSD1 NM_024333.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.51
• Publications: 2 publications found

Genes affected

FSD1 (HGNC:13745): (fibronectin type III and SPRY domain containing 1) This gene encodes a centrosome associated protein that is characterized by an N-terminal coiled-coil region downstream of B-box (BBC) domain, a central fibronectin type III domain, and a C-terminal repeats in splA and RyR (SPRY) domain. The encoded protein associates with a subset of microtubules and may be involved in the stability and organization of microtubules during cytokinesis. [provided by RefSeq, Apr 2009]

ENSG00000296069 (HGNC:):

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=0.22370875).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_024333.3. 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
	FSD1	NM_024333.3	MANE Select	c.263C>G	p.Thr88Arg	missense	Exon 4 of 13	NP_077309.1	Q9BTV5
	FSD1	NM_001330429.2		c.263C>G	p.Thr88Arg	missense	Exon 4 of 13	NP_001317358.1	M0R366

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FSD1	ENST00000221856.11	TSL:1 MANE Select	c.263C>G	p.Thr88Arg	missense	Exon 4 of 13	ENSP00000221856.5	Q9BTV5
	FSD1	ENST00000911582.1		c.263C>G	p.Thr88Arg	missense	Exon 4 of 13	ENSP00000581641.1
	FSD1	ENST00000911584.1		c.260C>G	p.Thr87Arg	missense	Exon 4 of 13	ENSP00000581643.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.24
BayesDel_addAF	Benign	-0.11	T
BayesDel_noAF	Benign	-0.39
CADD	Uncertain	23
DANN	Benign	0.97
DEOGEN2	Benign	0.036	T
Eigen	Benign	0.10
Eigen_PC	Benign	0.12
FATHMM_MKL	Uncertain	0.87	D
LIST_S2	Benign	0.82	T
M_CAP	Benign	0.028	D
MetaRNN	Benign	0.22	T
MetaSVM	Benign	-0.95	T
MutationAssessor	Uncertain	2.2	M
PhyloP100		2.5
PrimateAI	Uncertain	0.68	T
PROVEAN	Benign	0.0	N
REVEL	Benign	0.096
Sift	Benign	0.80	T
Sift4G	Benign	0.17	T
Polyphen		0.64	P
Vest4		0.41
MutPred		0.32		Gain of sheet (P = 0.039)
MVP		0.30
MPC		0.52
ClinPred		0.57	D
GERP RS		2.9
Varity_R		0.057
gMVP		0.57
Mutation Taster		=86/14	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: rs149694101; hg19: chr19-4307898;