4-161386389-C-T

Variant names:

• chr4-161386389-C-T
• rs750641663
• NM_020116.5:c.1902G>A

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_020116.5(FSTL5):​c.1902G>A​(p.Met634Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: FSTL5 NM_020116.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.26

Genes affected

FSTL5 (HGNC:21386): (follistatin like 5) Predicted to enable calcium ion binding activity. Predicted to be involved in cell differentiation. Predicted to be located in extracellular region. [provided by Alliance of Genome Resources, Apr 2022]

ENSG00000249568 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.2794428).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FSTL5	NM_020116.5	c.1902G>A	p.Met634Ile	missense_variant	Exon 16 of 16	ENST00000306100.10	NP_064501.2
FSTL5	NM_001128427.3	c.1899G>A	p.Met633Ile	missense_variant	Exon 16 of 16		NP_001121899.1
FSTL5	NM_001128428.3	c.1872G>A	p.Met624Ile	missense_variant	Exon 15 of 15		NP_001121900.1
FSTL5	XM_011532126.1	c.1875G>A	p.Met625Ile	missense_variant	Exon 15 of 15		XP_011530428.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FSTL5	ENST00000306100.10	c.1902G>A	p.Met634Ile	missense_variant	Exon 16 of 16	1	NM_020116.5	ENSP00000305334.4
FSTL5	ENST00000379164.8	c.1899G>A	p.Met633Ile	missense_variant	Exon 16 of 16	1		ENSP00000368462.4
FSTL5	ENST00000427802.2	c.1872G>A	p.Met624Ile	missense_variant	Exon 15 of 15	1		ENSP00000389270.2
ENSG00000249568	ENST00000508189.1	n.812C>T		non_coding_transcript_exon_variant	Exon 2 of 2	2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.50
BayesDel_addAF	Benign	-0.021	T
BayesDel_noAF	Benign	-0.27
CADD	Benign	22
DANN	Uncertain	0.99
DEOGEN2	Benign	0.013	T;.;.
Eigen	Uncertain	0.21
Eigen_PC	Uncertain	0.34
FATHMM_MKL	Uncertain	0.90	D
LIST_S2	Pathogenic	0.98	D;D;D
M_CAP	Benign	0.017	T
MetaRNN	Benign	0.28	T;T;T
MetaSVM	Uncertain	-0.21	T
MutationAssessor	Uncertain	2.3	M;.;.
PrimateAI	Uncertain	0.49	T
PROVEAN	Benign	-2.0	N;N;N
REVEL	Benign	0.19
Sift	Uncertain	0.015	D;D;D
Sift4G	Benign	0.14	T;T;T
Polyphen		0.077	B;.;.
Vest4		0.37
MutPred		0.41		Loss of sheet (P = 0.0181);.;.;
MVP		0.70
MPC		0.12
ClinPred		0.70	D
GERP RS		5.8
Varity_R		0.55
gMVP		0.48

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: rs750641663; hg19: chr4-162307541;