rs2031211682

Variant names:

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

Your query was ambiguous. Multiple possible variants found:

• chr19-676515-A-C
• chr19-676515-A-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>C​(p.Asn31Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000677 in 147,740 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. 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. N31I) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.0000068 (0 hom., cov: 31)
  • Exomes 𝑓: 0.0000052 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: FSTL3 NM_005860.3 missense
• Clinical Significance: Not reported in ClinVar
• 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=0.080155134).

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>C	p.Asn31Thr	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>C	p.Asn31Thr	missense	Exon 1 of 5	ENSP00000166139.3	O95633-1
	FSTL3	ENST00000905299.1		c.92A>C	p.Asn31Thr	missense	Exon 1 of 4	ENSP00000575358.1
	FSTL3	ENST00000964202.1		c.92A>C	p.Asn31Thr	missense	Exon 1 of 2	ENSP00000634261.1

Frequencies

GnomAD3 genomes AF: 0.00000677 AC: 1 AN: 147740 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000150

Gnomad OTH AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00000518 AC: 4 AN: 772130 Hom.: 0 Cov.: 17 AF XY: 0.0000110 AC XY: 4 AN XY: 364242

⚠️ 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: 11572

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

Ashkenazi Jewish (ASJ) AF: 0.000137 AC: 1 AN: 7306

East Asian (EAS) AF: 0.00 AC: 0 AN: 9482

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: 0.00000438 AC: 3 AN: 684208

Other (OTH) AF: 0.00 AC: 0 AN: 27894

⚠️ 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 AF: 0.00000677 AC: 1 AN: 147740 Hom.: 0 Cov.: 31 AF XY: 0.0000139 AC XY: 1 AN XY: 71996

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

African (AFR) AF: 0.00 AC: 0 AN: 40386

American (AMR) AF: 0.00 AC: 0 AN: 14966

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3404

East Asian (EAS) AF: 0.00 AC: 0 AN: 4912

South Asian (SAS) AF: 0.00 AC: 0 AN: 4720

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 9568

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 310

European-Non Finnish (NFE) AF: 0.0000150 AC: 1 AN: 66534

Other (OTH) AF: 0.00 AC: 0 AN: 2046

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.10
BayesDel_addAF	Benign	-0.35	T
BayesDel_noAF	Benign	-0.74
CADD	Benign	15
DANN	Benign	0.69
DEOGEN2	Benign	0.15	T
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.078	N
LIST_S2	Benign	0.31	T
M_CAP	Benign	0.018	T
MetaRNN	Benign	0.080	T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	0.90	L
PhyloP100		1.4
PrimateAI	Uncertain	0.72	T
PROVEAN	Benign	-1.1	N
REVEL	Benign	0.037
Sift	Benign	0.075	T
Sift4G	Benign	0.42	T
Polyphen		0.0	B
Vest4		0.14
MutPred		0.16		Gain of phosphorylation at N31 (P = 0.0412)
MVP		0.29
MPC		0.57
ClinPred		0.029	T
GERP RS		1.6
PromoterAI		0.073	Neutral
Varity_R		0.052
gMVP		0.54
Mutation Taster		=93/7	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;