19-681407-G-C

Variant names:

• chr19-681407-G-C
• ENST00000592947:c.-90G>C

Variant summary

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

The ENST00000592947(FSTL3):​c.-90G>C variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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)
• Consequence: FSTL3 ENST00000592947 5_prime_UTR_premature_start_codon_gain
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.610

Genes affected

FSTL3 (HGNC:3973): (follistatin like 3) Follistatin-like 3 is a secreted glycoprotein of the follistatin-module-protein family. It may have a role in leukemogenesis. [provided by RefSeq, Jul 2008]

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=0.20471549).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FSTL3	NM_005860.3	c.580G>C	p.Val194Leu	missense_variant	Exon 4 of 5	ENST00000166139.9	NP_005851.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FSTL3	ENST00000166139.9	c.580G>C	p.Val194Leu	missense_variant	Exon 4 of 5	1	NM_005860.3	ENSP00000166139.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Sep 26, 2022

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.580G>C (p.V194L) alteration is located in exon 4 (coding exon 4) of the FSTL3 gene. This alteration results from a G to C substitution at nucleotide position 580, causing the valine (V) at amino acid position 194 to be replaced by a leucine (L). 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	0.096
BayesDel_addAF	Benign	-0.32	T
BayesDel_noAF	Benign	-0.70
CADD	Benign	14
DANN	Benign	0.92
DEOGEN2	Benign	0.086	T;.
Eigen	Benign	-0.75
Eigen_PC	Benign	-0.67
FATHMM_MKL	Benign	0.48	N
LIST_S2	Benign	0.76	T;T
M_CAP	Benign	0.016	T
MetaRNN	Benign	0.20	T;T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	0.13	N;.
PrimateAI	Uncertain	0.62	T
PROVEAN	Benign	-0.13	N;.
REVEL	Benign	0.075
Sift	Benign	0.39	T;.
Sift4G	Benign	0.57	T;T
Polyphen		0.0	B;.
Vest4		0.28
MutPred		0.56		Loss of catalytic residue at V194 (P = 0.061);.;
MVP		0.50
MPC		0.55
ClinPred		0.091	T
GERP RS		-2.7
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.12
gMVP		0.62

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: chr19-681407;