Variant 4-161500098-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 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

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 made for transcript

Verdict is Uncertain_significance. Variant got 3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.753

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
FSTL5	NM_020116.5 linkuse as main transcript	c.1376A>G	p.Glu459Gly	missense_variant	12/16	ENST00000306100.10	NP_064501.2
FSTL5	NM_001128427.3 linkuse as main transcript	c.1373A>G	p.Glu458Gly	missense_variant	12/16		NP_001121899.1
FSTL5	NM_001128428.3 linkuse as main transcript	c.1346A>G	p.Glu449Gly	missense_variant	11/15		NP_001121900.1
FSTL5	XM_011532126.1 linkuse as main transcript	c.1349A>G	p.Glu450Gly	missense_variant	11/15		XP_011530428.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FSTL5	ENST00000306100.10 linkuse as main transcript	c.1376A>G	p.Glu459Gly	missense_variant	12/16	1	NM_020116.5	ENSP00000305334	P5	Q8N475-1
FSTL5	ENST00000379164.8 linkuse as main transcript	c.1373A>G	p.Glu458Gly	missense_variant	12/16	1		ENSP00000368462	A1	Q8N475-2
FSTL5	ENST00000427802.2 linkuse as main transcript	c.1346A>G	p.Glu449Gly	missense_variant	11/15	1		ENSP00000389270	A1	Q8N475-3
FSTL5	ENST00000511999.1 linkuse as main transcript			upstream_gene_variant		3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000123

AC:

AN:

244222

Hom.:

AF XY:

0.0000152

AC XY:

AN XY:

131948

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 SAS exome

AF:

0.0000336

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

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000117

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000181

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ExAC

AF:

0.00000824

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jan 03, 2024

The c.1376A>G (p.E459G) alteration is located in exon 12 (coding exon 11) of the FSTL5 gene. This alteration results from a A to G substitution at nucleotide position 1376, causing the glutamic acid (E) at amino acid position 459 to be replaced by a glycine (G). 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

0.23

BayesDel_addAF

Uncertain

0.047

BayesDel_noAF

Benign

-0.17

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.066

T;.;.

Eigen

Benign

0.058

Eigen_PC

Uncertain

0.24

FATHMM_MKL

Uncertain

0.94

LIST_S2

Uncertain

0.92

D;D;D

M_CAP

Benign

0.049

MetaRNN

Pathogenic

0.75

D;D;D

MetaSVM

Benign

-0.69

MutationAssessor

Benign

1.9

L;.;.

MutationTaster

Benign

1.0

D;D;D;D

PrimateAI

Uncertain

0.72

PROVEAN

Uncertain

-3.8

D;D;D

REVEL

Uncertain

0.37

Sift

Uncertain

0.0040

D;D;D

Sift4G

Uncertain

0.015

D;D;D

Polyphen

0.085

B;.;.

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

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over