4-161656423-C-A

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP3

The NM_020116.5(FSTL5):c.799G>T(p.Val267Phe) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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)
• Consequence: FSTL5 NM_020116.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.50

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]

ACMG classification

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, 0.785

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FSTL5	NM_020116.5	c.799G>T	p.Val267Phe	missense_variant	7/16	ENST00000306100.10
FSTL5	NM_001128427.3	c.796G>T	p.Val266Phe	missense_variant	7/16
FSTL5	NM_001128428.3	c.796G>T	p.Val266Phe	missense_variant	7/15
FSTL5	XM_011532126.1	c.799G>T	p.Val267Phe	missense_variant	7/15

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FSTL5	ENST00000306100.10	c.799G>T	p.Val267Phe	missense_variant	7/16	1	NM_020116.5	P5
FSTL5	ENST00000379164.8	c.796G>T	p.Val266Phe	missense_variant	7/16	1		A1
FSTL5	ENST00000427802.2	c.796G>T	p.Val266Phe	missense_variant	7/15	1		A1
FSTL5	ENST00000511170.1	n.161G>T		non_coding_transcript_exon_variant	2/5	4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 29

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Sep 12, 2023

The c.799G>T (p.V267F) alteration is located in exon 7 (coding exon 6) of the FSTL5 gene. This alteration results from a G to T substitution at nucleotide position 799, causing the valine (V) at amino acid position 267 to be replaced by a phenylalanine (F). 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	0.30
BayesDel_addAF	Pathogenic	0.19	D
BayesDel_noAF	Uncertain	0.030
Cadd	Uncertain	25
Dann	Uncertain	1.0
DEOGEN2	Benign	0.025	T;.;.
Eigen	Pathogenic	0.78
Eigen_PC	Pathogenic	0.76
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.96	D;D;D
M_CAP	Benign	0.064	D
MetaRNN	Pathogenic	0.79	D;D;D
MetaSVM	Benign	-0.88	T
MutationAssessor	Uncertain	2.6	M;.;.
MutationTaster	Benign	1.0	D;D;D;D
PrimateAI	Benign	0.48	T
PROVEAN	Uncertain	-2.9	D;D;D
REVEL	Uncertain	0.39
Sift	Uncertain	0.025	D;D;D
Sift4G	Uncertain	0.0020	D;D;D
Polyphen		0.72	P;.;.
Vest4		0.86
MutPred		0.44		Gain of sheet (P = 0.0085);.;.;
MVP		0.61
MPC		0.40
ClinPred		0.99	D
GERP RS		5.4
Varity_R		0.53
gMVP		0.70

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr4-162577575;