Genetic Variant FSTL5:p.Glu459Gly (chr4-161500098-T-C) – ACMG Classification: Uncertain_significance (3 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2PP3

The NM_020116.5(FSTL5):c.1376A>G(p.Glu459Gly) variant causes a missense change. The variant allele was found at a frequency of 0.00000206 in 1,454,426 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

FSTL5
NM_020116.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.89

Publications

1 publications found

Variant links:

Genes affected

FSTL5 (HGNC:21386): (follistatin like 5) Predicted to enable calcium ion binding activity. Predicted to be involved in cell differentiation. Predicted to be located in extracellular region. [provided by Alliance of Genome Resources, Apr 2022]

FSTL5 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.753

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_020116.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
FSTL5	NM_020116.5	MANE Select	c.1376A>G	p.Glu459Gly	missense	Exon 12 of 16	NP_064501.2	Q8N475-1
FSTL5	NM_001128427.3		c.1373A>G	p.Glu458Gly	missense	Exon 12 of 16	NP_001121899.1	Q8N475-2
FSTL5	NM_001128428.3		c.1346A>G	p.Glu449Gly	missense	Exon 11 of 15	NP_001121900.1	Q8N475-3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
FSTL5	ENST00000306100.10	TSL:1 MANE Select	c.1376A>G	p.Glu459Gly	missense	Exon 12 of 16	ENSP00000305334.4	Q8N475-1
FSTL5	ENST00000379164.8	TSL:1	c.1373A>G	p.Glu458Gly	missense	Exon 12 of 16	ENSP00000368462.4	Q8N475-2
FSTL5	ENST00000427802.2	TSL:1	c.1346A>G	p.Glu449Gly	missense	Exon 11 of 15	ENSP00000389270.2	Q8N475-3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.0000123

AC:

AN:

244222

AF XY:

0.0000152

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000907

Gnomad OTH exome

AF:

0.000168

GnomAD4 exome

AF:

0.00000206

AC:

AN:

1454426

Hom.:

Cov.:

AF XY:

0.00000415

AC XY:

AN XY:

723430

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33268

American (AMR)

AF:

0.00

AC:

AN:

44210

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25968

East Asian (EAS)

AF:

0.00

AC:

AN:

39384

South Asian (SAS)

AF:

0.0000117

AC:

AN:

85480

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53084

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5740

European-Non Finnish (NFE)

AF:

0.00000181

AC:

AN:

1107200

Other (OTH)

AF:

0.00

AC:

AN:

60092

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ExAC

AF:

0.00000824

AC:

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

0.23

BayesDel_addAF

Uncertain

0.047

BayesDel_noAF

Benign

-0.17

CADD

Uncertain

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.066

Eigen

Benign

0.058

Eigen_PC

Uncertain

0.24

FATHMM_MKL

Uncertain

0.94

LIST_S2

Uncertain

0.92

M_CAP

Benign

0.049

MetaRNN

Pathogenic

0.75

MetaSVM

Benign

-0.69

MutationAssessor

Benign

1.9

PhyloP100

5.9

PrimateAI

Uncertain

0.72

PROVEAN

Uncertain

-3.8

REVEL

Uncertain

0.37

Sift

Uncertain

0.0040

Sift4G

Uncertain

0.015

Polyphen

0.085

Vest4

0.74

MutPred

0.56

Gain of sheet (P = 0.0344)

MVP

0.77

MPC

0.37

ClinPred

0.94

GERP RS

5.3

Varity_R

0.27

gMVP

0.67

Mutation Taster

=83/17

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over