19-680304-G-A

Variant names:

• chr19-680304-G-A
• rs1238641305
• NM_005860.3:c.320G>A

Variant summary

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

The NM_005860.3(FSTL3):​c.320G>A​(p.Gly107Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000087 in 1,150,040 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 8.7e-7 (0 hom.)
• Consequence: FSTL3 NM_005860.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.33
• Publications: 1 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.320G>A	p.Gly107Asp	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.320G>A	p.Gly107Asp	missense	Exon 3 of 5	ENSP00000166139.3	O95633-1
	FSTL3	ENST00000905299.1		c.320G>A	p.Gly107Asp	missense	Exon 3 of 4	ENSP00000575358.1
	FSTL3	ENST00000589185.2	TSL:2	c.-14G>A		5_prime_UTR	Exon 1 of 2	ENSP00000484376.1	A0A087X1Q2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00 AC: 0 AN: 7962 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 8.70e-7 AC: 1 AN: 1150040 Hom.: 0 Cov.: 29 AF XY: 0.00000179 AC XY: 1 AN XY: 557754

African (AFR) AF: 0.00 AC: 0 AN: 22778

American (AMR) AF: 0.00 AC: 0 AN: 9164

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 15158

East Asian (EAS) AF: 0.00 AC: 0 AN: 25422

South Asian (SAS) AF: 0.00 AC: 0 AN: 41288

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 25844

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3108

European-Non Finnish (NFE) AF: 0.00000104 AC: 1 AN: 961362

Other (OTH) AF: 0.00 AC: 0 AN: 45916

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000113

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Pathogenic	0.20	D
BayesDel_noAF	Uncertain	0.060
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Uncertain	0.45	T
Eigen	Uncertain	0.22
Eigen_PC	Uncertain	0.24
FATHMM_MKL	Uncertain	0.77	D
LIST_S2	Uncertain	0.87	D
M_CAP	Pathogenic	0.72	D
MetaRNN	Uncertain	0.62	D
MetaSVM	Uncertain	0.58	D
MutationAssessor	Uncertain	2.1	M
PhyloP100		3.3
PrimateAI	Pathogenic	0.80	T
PROVEAN	Uncertain	-3.5	D
REVEL	Pathogenic	0.71
Sift	Benign	0.037	D
Sift4G	Benign	0.087	T
Polyphen		0.96	D
Vest4		0.22
MutPred		0.83		Gain of solvent accessibility (P = 0.0281)
MVP		0.95
MPC		0.81
ClinPred		0.97	D
GERP RS		3.6
PromoterAI		0.0056	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.73
gMVP		0.79
Mutation Taster		=53/47	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: rs1238641305; hg19: chr19-680304;