Variant chr4-161459234-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_020116.5(FSTL5):c.1694A>G(p.Glu565Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000249 in 1,608,230 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

FSTL5
NM_020116.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.04

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.24228597).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FSTL5	NM_020116.5 linkuse as main transcript	c.1694A>G	p.Glu565Gly	missense_variant	14/16	ENST00000306100.10	NP_064501.2	Q8N475-1
FSTL5	NM_001128427.3 linkuse as main transcript	c.1691A>G	p.Glu564Gly	missense_variant	14/16		NP_001121899.1	Q8N475-2
FSTL5	NM_001128428.3 linkuse as main transcript	c.1664A>G	p.Glu555Gly	missense_variant	13/15		NP_001121900.1	Q8N475-3
FSTL5	XM_011532126.1 linkuse as main transcript	c.1667A>G	p.Glu556Gly	missense_variant	13/15		XP_011530428.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
FSTL5	ENST00000306100.10 linkuse as main transcript	c.1694A>G	p.Glu565Gly	missense_variant	14/16	1	NM_020116.5	ENSP00000305334.4	Q8N475-1
FSTL5	ENST00000379164.8 linkuse as main transcript	c.1691A>G	p.Glu564Gly	missense_variant	14/16	1		ENSP00000368462.4	Q8N475-2
FSTL5	ENST00000427802.2 linkuse as main transcript	c.1664A>G	p.Glu555Gly	missense_variant	13/15	1		ENSP00000389270.2	Q8N475-3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000398

AC:

AN:

251330

Hom.:

AF XY:

0.00000736

AC XY:

AN XY:

135822

show subpopulations

Gnomad AFR exome

AF:

0.0000615

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000137

AC:

AN:

1455942

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

724658

show subpopulations

Gnomad4 AFR exome

AF:

0.0000600

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000131

AC:

AN:

152288

Hom.:

Cov.:

AF XY:

0.0000134

AC XY:

AN XY:

74456

show subpopulations

Gnomad4 AFR

AF:

0.0000481

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.00000756

Asia WGS

AF:

0.000289

AC:

AN:

3478

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

Sep 24, 2024

The c.1694A>G (p.E565G) alteration is located in exon 14 (coding exon 13) of the FSTL5 gene. This alteration results from a A to G substitution at nucleotide position 1694, causing the glutamic acid (E) at amino acid position 565 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

0.11

BayesDel_addAF

Benign

-0.24

BayesDel_noAF

Benign

-0.40

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.043

T;.;.

Eigen

Benign

0.082

Eigen_PC

Benign

0.21

FATHMM_MKL

Uncertain

0.94

LIST_S2

Benign

0.82

T;T;T

M_CAP

Benign

0.024

MetaRNN

Benign

0.24

T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.7

L;.;.

PrimateAI

Benign

0.42

PROVEAN

Uncertain

-3.0

D;D;D

REVEL

Benign

0.051

Sift

Benign

0.063

T;T;T

Sift4G

Benign

0.13

T;T;T

Polyphen

0.19

B;.;.

Vest4

0.39

MutPred

0.46

Loss of solvent accessibility (P = 0.0387);.;.;

MVP

0.59

MPC

0.062

ClinPred

0.72

GERP RS

5.4

Varity_R

0.21

gMVP

0.33

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