chr19-4306316-C-G

Variant names:

• chr19-4306316-C-G
• NM_024333.3:c.230C>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.230C>G​(p.Thr77Ser) 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. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 31)
• Consequence: FSD1 NM_024333.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.66
• Publications: 0 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=0.16110122).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FSD1	NM_024333.3	c.230C>G	p.Thr77Ser	missense_variant	Exon 3 of 13	ENST00000221856.11	NP_077309.1
FSD1	NM_001330429.2	c.230C>G	p.Thr77Ser	missense_variant	Exon 3 of 13		NP_001317358.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FSD1	ENST00000221856.11	c.230C>G	p.Thr77Ser	missense_variant	Exon 3 of 13	1	NM_024333.3	ENSP00000221856.5

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 31

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Jul 30, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.230C>G (p.T77S) alteration is located in exon 3 (coding exon 3) of the FSD1 gene. This alteration results from a C to G substitution at nucleotide position 230, causing the threonine (T) at amino acid position 77 to be replaced by a serine (S). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.16
BayesDel_addAF	Benign	-0.17	T
BayesDel_noAF	Benign	-0.48
CADD	Benign	21
DANN	Benign	0.90
DEOGEN2	Benign	0.031	T;T
Eigen	Benign	-0.23
Eigen_PC	Benign	-0.075
FATHMM_MKL	Uncertain	0.91	D
LIST_S2	Benign	0.64	T;T
M_CAP	Benign	0.012	T
MetaRNN	Benign	0.16	T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.1	L;.
PhyloP100		1.7
PrimateAI	Uncertain	0.64	T
PROVEAN	Benign	-0.39	N;.
REVEL	Benign	0.053
Sift	Benign	0.74	T;.
Sift4G	Benign	0.69	T;T
Polyphen		0.0060	B;.
Vest4		0.47
MutPred		0.31		Loss of helix (P = 0.0376);Loss of helix (P = 0.0376);
MVP		0.15
MPC		0.47
ClinPred		0.25	T
GERP RS		3.4
PromoterAI		0.0078	Neutral
Varity_R		0.091
gMVP		0.49
Mutation Taster		=95/5	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

hg19: chr19-4306313;