dbSNP rs1026348227: FSTL5:p.Phe472Cys (chr4-161500059-A-C) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_020116.5(FSTL5):c.1415T>G(p.Phe472Cys) variant causes a missense change. The variant allele was found at a frequency of 0.0000521 in 1,610,776 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000026 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000055 ( 0 hom. )

Consequence

FSTL5
NM_020116.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.89

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FSTL5	NM_020116.5 link	c.1415T>G	p.Phe472Cys	missense_variant	Exon 12 of 16	ENST00000306100.10	NP_064501.2	Q8N475-1
FSTL5	NM_001128427.3 link	c.1412T>G	p.Phe471Cys	missense_variant	Exon 12 of 16		NP_001121899.1	Q8N475-2
FSTL5	NM_001128428.3 link	c.1385T>G	p.Phe462Cys	missense_variant	Exon 11 of 15		NP_001121900.1	Q8N475-3
FSTL5	XM_011532126.1 link	c.1388T>G	p.Phe463Cys	missense_variant	Exon 11 of 15		XP_011530428.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
FSTL5	ENST00000306100.10 link	c.1415T>G	p.Phe472Cys	missense_variant	Exon 12 of 16	1	NM_020116.5	ENSP00000305334.4	Q8N475-1
FSTL5	ENST00000379164.8 link	c.1412T>G	p.Phe471Cys	missense_variant	Exon 12 of 16	1		ENSP00000368462.4	Q8N475-2
FSTL5	ENST00000427802.2 link	c.1385T>G	p.Phe462Cys	missense_variant	Exon 11 of 15	1		ENSP00000389270.2	Q8N475-3
FSTL5	ENST00000511999.1 link	n.16T>G		non_coding_transcript_exon_variant	Exon 1 of 2	3

Frequencies

GnomAD3 genomes

AF:

0.0000263

AC:

AN:

152136

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000588

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.0000548

AC:

AN:

1458640

Hom.:

Cov.:

AF XY:

0.0000579

AC XY:

AN XY:

725652

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:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000712

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

AF:

0.0000263

AC:

AN:

152136

Hom.:

Cov.:

AF XY:

0.0000404

AC XY:

AN XY:

74326

show subpopulations

Gnomad4 AFR

AF:

0.00

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:

0.0000588

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000712

Hom.:

Bravo

AF:

0.0000264

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Sep 27, 2021

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.1415T>G (p.F472C) alteration is located in exon 12 (coding exon 11) of the FSTL5 gene. This alteration results from a T to G substitution at nucleotide position 1415, causing the phenylalanine (F) at amino acid position 472 to be replaced by a cysteine (C). 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

Pathogenic

0.90

BayesDel_addAF

Uncertain

0.047

BayesDel_noAF

Benign

-0.17

CADD

Pathogenic

DANN

Uncertain

0.99

DEOGEN2

Benign

0.025

T;.;.

Eigen

Uncertain

0.40

Eigen_PC

Uncertain

0.49

FATHMM_MKL

Uncertain

0.96

LIST_S2

Uncertain

0.92

D;D;D

M_CAP

Benign

0.042

MetaRNN

Uncertain

0.71

D;D;D

MetaSVM

Benign

-0.39

MutationAssessor

Benign

0.90

L;.;.

PrimateAI

Uncertain

0.76

PROVEAN

Benign

-1.6

N;N;N

REVEL

Uncertain

0.39

Sift

Uncertain

0.010

D;D;D

Sift4G

Uncertain

0.0040

D;D;D

Polyphen

0.98

D;.;.

Vest4

0.69

MutPred

0.43

Gain of ubiquitination at K477 (P = 0.0837);.;.;

MVP

0.84

MPC

0.41

ClinPred

0.93

GERP RS

5.3

Varity_R

0.14

gMVP

0.58

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