19-680361-C-G

Variant names:

• chr19-680361-C-G
• rs768914737
• NM_005860.3:c.377C>G

Variant summary

Our verdict is Uncertain significance. The variant received 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. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. S126L) has been classified as Uncertain significance.

• 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
• Publications: 0 publications found

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

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005860.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FSTL3	NM_005860.3	MANE Select	c.377C>G	p.Ser126Trp	missense	Exon 3 of 5	NP_005851.1	O95633-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FSTL3	ENST00000166139.9	TSL:1 MANE Select	c.377C>G	p.Ser126Trp	missense	Exon 3 of 5	ENSP00000166139.3	O95633-1
	FSTL3	ENST00000905299.1		c.377C>G	p.Ser126Trp	missense	Exon 3 of 4	ENSP00000575358.1
	FSTL3	ENST00000589185.2	TSL:2	c.44C>G	p.Ser15Trp	missense	Exon 1 of 2	ENSP00000484376.1	A0A087X1Q2

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

African (AFR) AF: 0.00 AC: 0 AN: 22820

American (AMR) AF: 0.00 AC: 0 AN: 8520

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 14800

East Asian (EAS) AF: 0.00 AC: 0 AN: 26184

South Asian (SAS) AF: 0.00 AC: 0 AN: 34810

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 24630

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3034

European-Non Finnish (NFE) AF: 0.00000105 AC: 1 AN: 948556

Other (OTH) AF: 0.00 AC: 0 AN: 45442

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

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
M_CAP	Pathogenic	0.80	D
MetaRNN	Uncertain	0.64	D
MetaSVM	Uncertain	-0.28	T
MutationAssessor	Pathogenic	3.2	M
PhyloP100		3.6
PrimateAI	Pathogenic	0.88	D
PROVEAN	Pathogenic	-4.4	D
REVEL	Benign	0.25
Sift	Uncertain	0.0010	D
Sift4G	Pathogenic	0.0010	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
PromoterAI		-0.056	Neutral
Varity_R		0.50
gMVP		0.38
Mutation Taster		=63/37	polymorphism

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

Other links and lift over

dbSNP: rs768914737; hg19: chr19-680361;