3-120402878-C-G

Variant names:

• chr3-120402878-C-G
• NM_007085.5:c.735G>C

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_007085.5(FSTL1):​c.735G>C​(p.Glu245Asp) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. 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. E245K) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 31)
• Consequence: FSTL1 NM_007085.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.58

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:52935): (butyrophilin like 12, pseudogene)

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FSTL1	NM_007085.5	c.735G>C	p.Glu245Asp	missense_variant	Exon 9 of 11	ENST00000295633.8	NP_009016.1
BTNL12P	NR_187254.1	n.997-12923C>G		intron_variant	Intron 3 of 4
BTNL12P	NR_187255.1	n.997-12923C>G		intron_variant	Intron 3 of 4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FSTL1	ENST00000295633.8	c.735G>C	p.Glu245Asp	missense_variant	Exon 9 of 11	1	NM_007085.5	ENSP00000295633.3

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 31

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Dec 17, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.735G>C (p.E245D) alteration is located in exon 9 (coding exon 8) of the FSTL1 gene. This alteration results from a G to C substitution at nucleotide position 735, causing the glutamic acid (E) at amino acid position 245 to be replaced by an aspartic acid (D). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.66
BayesDel_addAF	Uncertain	0.069	T
BayesDel_noAF	Benign	-0.14
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.32	T;.
Eigen	Uncertain	0.32
Eigen_PC	Uncertain	0.30
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.95	D;D
M_CAP	Benign	0.043	D
MetaRNN	Uncertain	0.68	D;D
MetaSVM	Benign	-0.32	T
MutationAssessor	Benign	1.8	L;.
PrimateAI	Uncertain	0.69	T
PROVEAN	Benign	-1.7	N;N
REVEL	Benign	0.26
Sift	Uncertain	0.016	D;T
Sift4G	Uncertain	0.017	D;D
Polyphen		0.93	P;.
Vest4		0.78
MutPred		0.32		Gain of glycosylation at Y240 (P = 0.0035);.;
MVP		0.70
MPC		0.66
ClinPred		0.89	D
GERP RS		4.8
Varity_R		0.25
gMVP		0.77

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr3-120121725;