4-161459235-C-T

Variant names:

• chr4-161459235-C-T
• NM_020116.5:c.1693G>A

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_020116.5(FSTL5):​c.1693G>A​(p.Glu565Lys) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: FSTL5 NM_020116.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.66

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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.36374238).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FSTL5	NM_020116.5	c.1693G>A	p.Glu565Lys	missense_variant	Exon 14 of 16	ENST00000306100.10	NP_064501.2
FSTL5	NM_001128427.3	c.1690G>A	p.Glu564Lys	missense_variant	Exon 14 of 16		NP_001121899.1
FSTL5	NM_001128428.3	c.1663G>A	p.Glu555Lys	missense_variant	Exon 13 of 15		NP_001121900.1
FSTL5	XM_011532126.1	c.1666G>A	p.Glu556Lys	missense_variant	Exon 13 of 15		XP_011530428.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FSTL5	ENST00000306100.10	c.1693G>A	p.Glu565Lys	missense_variant	Exon 14 of 16	1	NM_020116.5	ENSP00000305334.4
FSTL5	ENST00000379164.8	c.1690G>A	p.Glu564Lys	missense_variant	Exon 14 of 16	1		ENSP00000368462.4
FSTL5	ENST00000427802.2	c.1663G>A	p.Glu555Lys	missense_variant	Exon 13 of 15	1		ENSP00000389270.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1457446 Hom.: 0 Cov.: 28 AF XY: 0.00 AC XY: 0 AN XY: 725320

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: 0.00

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

Nov 24, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.1693G>A (p.E565K) alteration is located in exon 14 (coding exon 13) of the FSTL5 gene. This alteration results from a G to A substitution at nucleotide position 1693, causing the glutamic acid (E) at amino acid position 565 to be replaced by a lysine (K). 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	0.12
BayesDel_addAF	Benign	-0.089	T
BayesDel_noAF	Benign	-0.36
CADD	Benign	22
DANN	Uncertain	1.0
DEOGEN2	Benign	0.0030	T;.;.
Eigen	Benign	0.16
Eigen_PC	Uncertain	0.32
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Uncertain	0.91	D;D;D
M_CAP	Benign	0.016	T
MetaRNN	Benign	0.36	T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.4	L;.;.
PrimateAI	Uncertain	0.53	T
PROVEAN	Benign	-0.99	N;N;N
REVEL	Benign	0.11
Sift	Benign	0.34	T;T;T
Sift4G	Benign	0.33	T;T;T
Polyphen		0.19	B;.;.
Vest4		0.51
MutPred		0.55		Gain of MoRF binding (P = 0.0165);.;.;
MVP		0.56
MPC		0.062
ClinPred		0.92	D
GERP RS		5.4
Varity_R		0.24
gMVP		0.29

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: chr4-162380387;