chr5-133199528-C-A

Variant names:

• chr5-133199528-C-A
• rs149501035
• NM_015082.2:c.2096G>T

Variant summary

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

The NM_015082.2(FSTL4):​c.2096G>T​(p.Arg699Leu) variant causes a missense change. The variant allele was found at a frequency of 0.0000131 in 152,210 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.000013 (0 hom., cov: 32)
• Consequence: FSTL4 NM_015082.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.84

Genes affected

FSTL4 (HGNC:21389): (follistatin like 4) Predicted to enable brain-derived neurotrophic factor binding activity and calcium ion binding activity. Predicted to be involved in cell differentiation. Predicted to act upstream of or within negative regulation of brain-derived neurotrophic factor receptor signaling pathway; negative regulation of collateral sprouting; and negative regulation of dendritic spine development. Predicted to be located in extracellular region and secretory granule. [provided by Alliance of Genome Resources, Apr 2022]

ENSG00000248245 (HGNC:):

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
FSTL4	NM_015082.2	c.2096G>T	p.Arg699Leu	missense_variant	Exon 16 of 16	ENST00000265342.12	NP_055897.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FSTL4	ENST00000265342.12	c.2096G>T	p.Arg699Leu	missense_variant	Exon 16 of 16	5	NM_015082.2	ENSP00000265342.7
FSTL4	ENST00000509525.5	n.1314G>T		non_coding_transcript_exon_variant	Exon 8 of 8	2
ENSG00000248245	ENST00000509051.1	n.76-8308C>A		intron_variant	Intron 1 of 3	4
FSTL4	ENST00000511375.1	n.*205G>T		downstream_gene_variant		4

Frequencies

GnomAD3 genomes AF: 0.0000131 AC: 2 AN: 152210 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000483

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: 0.00

Gnomad OTH AF: 0.00

GnomAD3 exomes AF: 0.00000398 AC: 1 AN: 251170 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 135750

Gnomad AFR exome AF: 0.0000617

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome Cov.: 33

GnomAD4 genome AF: 0.0000131 AC: 2 AN: 152210 Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1 AN XY: 74344

Gnomad4 AFR AF: 0.0000483

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00

Gnomad4 OTH AF: 0.00

Bravo AF: 0.00000756

ExAC AF: 0.00000824 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.29
BayesDel_addAF	Benign	-0.17	T
BayesDel_noAF	Benign	-0.31
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.69	D;.
Eigen	Uncertain	0.39
Eigen_PC	Uncertain	0.28
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Uncertain	0.89	D;D
M_CAP	Uncertain	0.11	D
MetaRNN	Uncertain	0.74	D;D
MetaSVM	Benign	-0.87	T
MutationAssessor	Pathogenic	3.0	M;.
PrimateAI	Benign	0.38	T
PROVEAN	Pathogenic	-5.1	D;.
REVEL	Benign	0.25
Sift	Uncertain	0.0050	D;.
Sift4G	Uncertain	0.030	D;D
Polyphen		0.99	D;.
Vest4		0.61
MutPred		0.48		Loss of disorder (P = 0.045);.;
MVP		0.33
MPC		0.89
ClinPred		0.98	D
GERP RS		2.5
Varity_R		0.31
gMVP		0.82

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

Publications

LitVar

Other links and lift over

dbSNP: rs149501035; hg19: chr5-132535220;