Genetic Variant NM_024333.3:c.14G>A (chr19-4304760-G-A) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_024333.3(FSD1):c.14G>A(p.Arg5Lys) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000001 in 995,230 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/24 in silico tools predict a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 31)

Exomes 𝑓: 0.0000010 ( 0 hom. )

Consequence

FSD1
NM_024333.3 missense, splice_region

Scores

Splicing: ADA: 0.004072

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.680

Publications

0 publications found

Variant links:

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]

FSD1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.03001675).

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.14G>A	p.Arg5Lys	missense splice_region	Exon 1 of 13	NP_077309.1	Q9BTV5
	FSD1	NM_001330429.2		c.14G>A	p.Arg5Lys	missense splice_region	Exon 1 of 13	NP_001317358.1	M0R366

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
FSD1	ENST00000221856.11	TSL:1 MANE Select	c.14G>A	p.Arg5Lys	missense splice_region	Exon 1 of 13	ENSP00000221856.5	Q9BTV5
FSD1	ENST00000911582.1		c.14G>A	p.Arg5Lys	missense splice_region	Exon 1 of 13	ENSP00000581641.1
FSD1	ENST00000911584.1		c.14G>A	p.Arg5Lys	missense splice_region	Exon 1 of 13	ENSP00000581643.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000100

AC:

AN:

995230

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

472038

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

21392

American (AMR)

AF:

0.00

AC:

AN:

8256

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

13816

East Asian (EAS)

AF:

0.00

AC:

AN:

26094

South Asian (SAS)

AF:

0.00

AC:

AN:

17854

European-Finnish (FIN)

AF:

0.00

AC:

AN:

21126

Middle Eastern (MID)

AF:

0.00

AC:

AN:

2898

European-Non Finnish (NFE)

AF:

0.00000119

AC:

AN:

842958

Other (OTH)

AF:

0.00

AC:

AN:

40836

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.575

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.099

BayesDel_addAF

Benign

-0.27

BayesDel_noAF

Benign

-0.63

CADD

Benign

(source)

DANN

Benign

0.96

DEOGEN2

Benign

0.024

Eigen

Benign

-0.90

Eigen_PC

Benign

-0.70

FATHMM_MKL

Benign

0.34

LIST_S2

Benign

0.23

M_CAP

Uncertain

0.19

MetaRNN

Benign

0.030

MetaSVM

Benign

-0.97

MutationAssessor

Benign

-1.7

PhyloP100

0.68

PrimateAI

Uncertain

0.70

PROVEAN

Benign

0.72

REVEL

Benign

0.041

Sift

Benign

1.0

Sift4G

Benign

1.0

Polyphen

0.0

Vest4

0.093

MutPred

0.47

Gain of methylation at R5 (P = 0.0199)

MVP

0.043

MPC

0.46

ClinPred

0.081

GERP RS

0.87

PromoterAI

0.078

Neutral

(source)

Varity_R

0.10

gMVP

0.41

Mutation Taster

=69/31

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.0041

dbscSNV1_RF

Benign

0.25

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

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over