chr19-676515-A-T

Variant names:

• chr19-676515-A-T
• rs2031211682
• NM_005860.3:c.92A>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_005860.3(FSTL3):​c.92A>T​(p.Asn31Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000013 in 772,074 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. N31Y) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 0.0000013 (0 hom.)
• Consequence: FSTL3 NM_005860.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.39
• 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]

ENSG00000308766 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.106943846).

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.92A>T	p.Asn31Ile	missense	Exon 1 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.92A>T	p.Asn31Ile	missense	Exon 1 of 5	ENSP00000166139.3	O95633-1
	FSTL3	ENST00000905299.1		c.92A>T	p.Asn31Ile	missense	Exon 1 of 4	ENSP00000575358.1
	FSTL3	ENST00000964202.1		c.92A>T	p.Asn31Ile	missense	Exon 1 of 2	ENSP00000634261.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 0.00000130 AC: 1 AN: 772074 Hom.: 0 Cov.: 17 AF XY: 0.00 AC XY: 0 AN XY: 364234

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 11570

American (AMR) AF: 0.00 AC: 0 AN: 3994

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 7306

East Asian (EAS) AF: 0.00 AC: 0 AN: 9484

South Asian (SAS) AF: 0.00 AC: 0 AN: 14722

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 11134

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 1818

European-Non Finnish (NFE) AF: 0.00000146 AC: 1 AN: 684154

Other (OTH) AF: 0.00 AC: 0 AN: 27892

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 31

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	0.15
BayesDel_addAF	Benign	-0.30	T
BayesDel_noAF	Benign	-0.67
CADD	Benign	16
DANN	Benign	0.86
DEOGEN2	Benign	0.23	T
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.092	N
LIST_S2	Benign	0.36	T
M_CAP	Benign	0.035	D
MetaRNN	Benign	0.11	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.90	L
PhyloP100		1.4
PrimateAI	Uncertain	0.72	T
PROVEAN	Benign	-1.9	N
REVEL	Benign	0.047
Sift	Uncertain	0.016	D
Sift4G	Benign	0.15	T
Polyphen		0.0010	B
Vest4		0.20
MutPred		0.20		Loss of disorder (P = 0.0432)
MVP		0.42
MPC		0.74
ClinPred		0.059	T
GERP RS		1.6
PromoterAI		0.035	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
Varity_R		0.13
gMVP		0.65
Mutation Taster		=92/8	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: rs2031211682; hg19: chr19-676515;