Variant 4-161386103-C-T 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.2188G>A(p.Ala730Thr) variant causes a missense change. The variant allele was found at a frequency of 0.00000889 in 1,461,750 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: not found (cov: 32)

Exomes 𝑓: 0.0000089 ( 0 hom. )

Consequence

FSTL5
NM_020116.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.86

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:

ENSG00000249568 (HGNC:):

ENSG00000249568 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=0.11987543).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FSTL5	NM_020116.5 linkuse as main transcript	c.2188G>A	p.Ala730Thr	missense_variant	16/16	ENST00000306100.10	NP_064501.2	Q8N475-1
FSTL5	NM_001128427.3 linkuse as main transcript	c.2185G>A	p.Ala729Thr	missense_variant	16/16		NP_001121899.1	Q8N475-2
FSTL5	NM_001128428.3 linkuse as main transcript	c.2158G>A	p.Ala720Thr	missense_variant	15/15		NP_001121900.1	Q8N475-3
FSTL5	XM_011532126.1 linkuse as main transcript	c.2161G>A	p.Ala721Thr	missense_variant	15/15		XP_011530428.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
FSTL5	ENST00000306100.10 linkuse as main transcript	c.2188G>A	p.Ala730Thr	missense_variant	16/16	1	NM_020116.5	ENSP00000305334.4	Q8N475-1
FSTL5	ENST00000379164.8 linkuse as main transcript	c.2185G>A	p.Ala729Thr	missense_variant	16/16	1		ENSP00000368462.4	Q8N475-2
FSTL5	ENST00000427802.2 linkuse as main transcript	c.2158G>A	p.Ala720Thr	missense_variant	15/15	1		ENSP00000389270.2	Q8N475-3
ENSG00000249568	ENST00000508189.1 linkuse as main transcript	n.526C>T		non_coding_transcript_exon_variant	2/2	2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000319

AC:

AN:

250672

Hom.:

AF XY:

0.0000295

AC XY:

AN XY:

135452

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000164

Gnomad SAS exome

AF:

0.000163

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000889

AC:

AN:

1461750

Hom.:

Cov.:

AF XY:

0.00000825

AC XY:

AN XY:

727184

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000504

Gnomad4 SAS exome

AF:

0.000116

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Alfa

AF:

0.0000936

Hom.:

Bravo

AF:

0.00000756

ExAC

AF:

0.0000247

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3476

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

Dec 05, 2024

The c.2188G>A (p.A730T) alteration is located in exon 16 (coding exon 15) of the FSTL5 gene. This alteration results from a G to A substitution at nucleotide position 2188, causing the alanine (A) at amino acid position 730 to be replaced by a threonine (T). 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

0.10

BayesDel_addAF

Benign

-0.43

BayesDel_noAF

Benign

-0.59

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.0037

T;.;.

Eigen

Benign

-0.14

Eigen_PC

Benign

-0.047

FATHMM_MKL

Uncertain

0.87

LIST_S2

Benign

0.83

T;T;T

M_CAP

Benign

0.0087

MetaRNN

Benign

0.12

T;T;T

MetaSVM

Benign

-0.99

MutationAssessor

Benign

1.9

L;.;.

PrimateAI

Benign

0.43

PROVEAN

Benign

-0.97

N;N;N

REVEL

Benign

0.075

Sift

Benign

0.48

T;T;T

Sift4G

Benign

0.44

T;T;T

Polyphen

0.10

B;.;.

Vest4

0.052

MutPred

0.36

Loss of sheet (P = 0.0228);.;.;

MVP

0.40

MPC

0.31

ClinPred

0.084

GERP RS

4.8

Varity_R

0.11

gMVP

0.36

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

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