19-680444-C-T

Variant names:

• chr19-680444-C-T
• rs1367177915
• NM_005860.3:c.460C>T

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_005860.3(FSTL3):​c.460C>T​(p.Arg154Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000009 in 1,111,162 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. R154S) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 9.0e-7 (0 hom.)
• Consequence: FSTL3 NM_005860.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.43
• 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.460C>T	p.Arg154Cys	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.460C>T	p.Arg154Cys	missense	Exon 3 of 5	ENSP00000166139.3	O95633-1
	FSTL3	ENST00000905299.1		c.460C>T	p.Arg154Cys	missense	Exon 3 of 4	ENSP00000575358.1
	FSTL3	ENST00000589185.2	TSL:2	c.127C>T	p.Arg43Cys	missense	Exon 1 of 2	ENSP00000484376.1	A0A087X1Q2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 9.00e-7 AC: 1 AN: 1111162 Hom.: 0 Cov.: 33 AF XY: 0.00000189 AC XY: 1 AN XY: 530406

African (AFR) AF: 0.00 AC: 0 AN: 22932

American (AMR) AF: 0.00 AC: 0 AN: 8448

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 14642

East Asian (EAS) AF: 0.0000375 AC: 1 AN: 26672

South Asian (SAS) AF: 0.00 AC: 0 AN: 29174

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 22952

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3000

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 938560

Other (OTH) AF: 0.00 AC: 0 AN: 44782

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.58
BayesDel_addAF	Benign	-0.10	T
BayesDel_noAF	Benign	-0.39
CADD	Pathogenic	32
DANN	Uncertain	1.0
DEOGEN2	Benign	0.25	T
Eigen	Uncertain	0.59
Eigen_PC	Uncertain	0.49
FATHMM_MKL	Benign	0.75	D
LIST_S2	Pathogenic	0.98	D
M_CAP	Pathogenic	0.79	D
MetaRNN	Uncertain	0.66	D
MetaSVM	Benign	-1.2	T
MutationAssessor	Uncertain	2.7	M
PhyloP100		1.4
PrimateAI	Pathogenic	0.87	D
PROVEAN	Pathogenic	-4.7	D
REVEL	Benign	0.18
Sift	Uncertain	0.0010	D
Sift4G	Uncertain	0.030	D
Polyphen		1.0	D
Vest4		0.27
MutPred		0.60		Loss of MoRF binding (P = 0.0247)
MVP		0.71
MPC		0.99
ClinPred		1.0	D
GERP RS		3.2
PromoterAI		-0.034	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.74
gMVP		0.70
Mutation Taster		=78/22	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: rs1367177915; hg19: chr19-680444;