3-120402871-C-G

Variant names:

• chr3-120402871-C-G
• rs753729548
• NM_007085.5:c.742G>C

Variant summary

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

The NM_007085.5(FSTL1):​c.742G>C​(p.Val248Leu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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. V248M) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 31)
• Consequence: FSTL1 NM_007085.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.43
• Publications: 0 publications found

Genes affected

FSTL1 (HGNC:3972): (follistatin like 1) This gene encodes a protein with similarity to follistatin, an activin-binding protein. It contains an FS module, a follistatin-like sequence containing 10 conserved cysteine residues. This gene product is thought to be an autoantigen associated with rheumatoid arthritis. [provided by RefSeq, Jul 2008]

BTNL12P (HGNC:):

BTNL12P (HGNC:52935): (butyrophilin like 12, pseudogene)

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_007085.5. 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
	FSTL1	NM_007085.5	MANE Select	c.742G>C	p.Val248Leu	missense	Exon 9 of 11	NP_009016.1	Q12841-1
	BTNL12P	NR_187254.1		n.997-12930C>G		intron	N/A
	BTNL12P	NR_187255.1		n.997-12930C>G		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FSTL1	ENST00000295633.8	TSL:1 MANE Select	c.742G>C	p.Val248Leu	missense	Exon 9 of 11	ENSP00000295633.3	Q12841-1
	FSTL1	ENST00000875454.1		c.766G>C	p.Val256Leu	missense	Exon 9 of 11	ENSP00000545513.1
	FSTL1	ENST00000955575.1		c.766G>C	p.Val256Leu	missense	Exon 8 of 10	ENSP00000625634.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.52
BayesDel_addAF	Uncertain	0.12	D
BayesDel_noAF	Uncertain	-0.060
CADD	Pathogenic	26
DANN	Uncertain	1.0
DEOGEN2	Benign	0.22	T
Eigen	Uncertain	0.34
Eigen_PC	Uncertain	0.39
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.95	D
M_CAP	Benign	0.029	D
MetaRNN	Uncertain	0.69	D
MetaSVM	Benign	-0.75	T
MutationAssessor	Benign	1.7	L
PhyloP100		7.4
PrimateAI	Uncertain	0.67	T
PROVEAN	Benign	-0.91	N
REVEL	Benign	0.14
Sift	Uncertain	0.015	D
Sift4G	Uncertain	0.023	D
Polyphen		0.94	P
Vest4		0.89
MutPred		0.34		Loss of sheet (P = 0.0025)
MVP		0.66
MPC		0.24
ClinPred		0.86	D
GERP RS		4.8
PromoterAI		-0.0032	Neutral
Varity_R		0.27
gMVP		0.71
Mutation Taster		=58/42	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: rs753729548; hg19: chr3-120121718;