19-680361-C-G

Variant names:

• chr19-680361-C-G
• NM_005860.3:c.377C>G

Variant summary

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

The NM_005860.3(FSTL3):​c.377C>G​(p.Ser126Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000886 in 1,128,796 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 8.9e-7 (0 hom.)
• Consequence: FSTL3 NM_005860.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.57

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 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
FSTL3	NM_005860.3	c.377C>G	p.Ser126Trp	missense_variant	Exon 3 of 5	ENST00000166139.9	NP_005851.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FSTL3	ENST00000166139.9	c.377C>G	p.Ser126Trp	missense_variant	Exon 3 of 5	1	NM_005860.3	ENSP00000166139.3
FSTL3	ENST00000589185.2	c.44C>G	p.Ser15Trp	missense_variant	Exon 1 of 2	2		ENSP00000484376.1
FSTL3	ENST00000592058.3	n.111C>G		non_coding_transcript_exon_variant	Exon 2 of 4	5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 8.86e-7 AC: 1 AN: 1128796 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 541946

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: 0.00000105

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.23
BayesDel_addAF	Benign	-0.046	T
BayesDel_noAF	Benign	-0.30
CADD	Benign	23
DANN	Uncertain	0.98
DEOGEN2	Uncertain	0.47	T;.
Eigen	Benign	-0.0049
Eigen_PC	Benign	-0.22
FATHMM_MKL	Uncertain	0.76	D
LIST_S2	Benign	0.79	T;T
M_CAP	Pathogenic	0.80	D
MetaRNN	Uncertain	0.64	D;D
MetaSVM	Uncertain	-0.28	T
MutationAssessor	Pathogenic	3.2	M;.
PrimateAI	Pathogenic	0.88	D
PROVEAN	Pathogenic	-4.4	D;.
REVEL	Benign	0.25
Sift	Uncertain	0.0010	D;.
Sift4G	Pathogenic	0.0010	D;D
Polyphen		1.0	D;.
Vest4		0.30
MutPred		0.51		Gain of catalytic residue at S126 (P = 0.001);.;
MVP		0.87
MPC		1.7
ClinPred		1.0	D
GERP RS		0.99
Varity_R		0.50
gMVP		0.38

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: chr19-680361;