19-4311985-C-A

Variant names:

• chr19-4311985-C-A
• rs376221601
• NM_024333.3:c.634C>A

Variant summary

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

The NM_024333.3(FSD1):​c.634C>A​(p.Arg212Ser) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. 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. R212C) 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: 3.62
• 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]

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

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.634C>A	p.Arg212Ser	missense	Exon 7 of 13	NP_077309.1	Q9BTV5
	FSD1	NM_001330429.2		c.634C>A	p.Arg212Ser	missense	Exon 7 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.634C>A	p.Arg212Ser	missense	Exon 7 of 13	ENSP00000221856.5	Q9BTV5
	FSD1	ENST00000598179.1	TSL:1	n.513C>A		non_coding_transcript_exon	Exon 1 of 7
	FSD1	ENST00000911582.1		c.634C>A	p.Arg212Ser	missense	Exon 7 of 13	ENSP00000581641.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.86
BayesDel_addAF	Uncertain	0.012	T
BayesDel_noAF	Benign	-0.22
CADD	Pathogenic	26
DANN	Uncertain	1.0
DEOGEN2	Benign	0.072	T
Eigen	Uncertain	0.37
Eigen_PC	Uncertain	0.32
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Benign	0.83	T
M_CAP	Uncertain	0.14	D
MetaRNN	Uncertain	0.61	D
MetaSVM	Benign	-0.31	T
MutationAssessor	Uncertain	2.3	M
PhyloP100		3.6
PrimateAI	Uncertain	0.62	T
PROVEAN	Uncertain	-2.5	N
REVEL	Uncertain	0.36
Sift	Benign	0.038	D
Sift4G	Uncertain	0.014	D
Polyphen		0.99	D
Vest4		0.61
MutPred		0.40		Gain of glycosylation at R212 (P = 0.0737)
MVP		0.31
MPC		1.4
ClinPred		0.95	D
GERP RS		3.6
Varity_R		0.42
gMVP		0.71
Mutation Taster		=39/61	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: rs376221601; hg19: chr19-4311982;