4-161385752-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_020116.5(FSTL5):c.2539G>A(p.Ala847Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000014 in 1,425,648 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: FSTL5 NM_020116.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.55

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]

(HGNC:):

ACMG classification

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=0.22885457).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FSTL5	NM_020116.5	c.2539G>A	p.Ala847Thr	missense_variant	16/16	ENST00000306100.10
FSTL5	NM_001128427.3	c.2536G>A	p.Ala846Thr	missense_variant	16/16
FSTL5	NM_001128428.3	c.2509G>A	p.Ala837Thr	missense_variant	15/15
FSTL5	XM_011532126.1	c.2512G>A	p.Ala838Thr	missense_variant	15/15

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FSTL5	ENST00000306100.10	c.2539G>A	p.Ala847Thr	missense_variant	16/16	1	NM_020116.5	P5
FSTL5	ENST00000379164.8	c.2536G>A	p.Ala846Thr	missense_variant	16/16	1		A1
FSTL5	ENST00000427802.2	c.2509G>A	p.Ala837Thr	missense_variant	15/15	1		A1
	ENST00000508189.1	n.254-79C>T		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000140 AC: 2 AN: 1425648 Hom.: 0 Cov.: 28 AF XY: 0.00000141 AC XY: 1 AN XY: 708224

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: 0.00000183

Gnomad4 OTH exome AF: 0.00

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

Dec 19, 2023

The c.2539G>A (p.A847T) 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 2539, causing the alanine (A) at amino acid position 847 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	0.088
BayesDel_addAF	Uncertain	0.033	T
BayesDel_noAF	Benign	-0.19
Cadd	Benign	23
Dann	Uncertain	1.0
DEOGEN2	Benign	0.0066	T;.;.
Eigen	Uncertain	0.36
Eigen_PC	Uncertain	0.48
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.96	D;D;D
M_CAP	Benign	0.016	T
MetaRNN	Benign	0.23	T;T;T
MetaSVM	Benign	-0.44	T
MutationAssessor	Uncertain	2.0	M;.;.
MutationTaster	Benign	1.0	D;D;D;D
PrimateAI	Uncertain	0.53	T
PROVEAN	Benign	-0.65	N;N;N
REVEL	Benign	0.18
Sift	Uncertain	0.013	D;D;D
Sift4G	Uncertain	0.019	D;D;D
Polyphen		0.91	P;.;.
Vest4		0.32
MutPred		0.30		Loss of sheet (P = 0.0037);.;.;
MVP		0.75
MPC		0.35
ClinPred		0.94	D
GERP RS		5.8
Varity_R		0.13
gMVP		0.52

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: chr4-162306904;