4-161385900-G-C

Variant names:

• chr4-161385900-G-C
• NM_020116.5:c.2391C>G

Variant summary

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

The NM_020116.5(FSTL5):​c.2391C>G​(p.Asn797Lys) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: FSTL5 NM_020116.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.00

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 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
FSTL5	NM_020116.5	c.2391C>G	p.Asn797Lys	missense_variant	Exon 16 of 16	ENST00000306100.10	NP_064501.2
FSTL5	NM_001128427.3	c.2388C>G	p.Asn796Lys	missense_variant	Exon 16 of 16		NP_001121899.1
FSTL5	NM_001128428.3	c.2361C>G	p.Asn787Lys	missense_variant	Exon 15 of 15		NP_001121900.1
FSTL5	XM_011532126.1	c.2364C>G	p.Asn788Lys	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.2391C>G	p.Asn797Lys	missense_variant	Exon 16 of 16	1	NM_020116.5	ENSP00000305334.4
FSTL5	ENST00000379164.8	c.2388C>G	p.Asn796Lys	missense_variant	Exon 16 of 16	1		ENSP00000368462.4
FSTL5	ENST00000427802.2	c.2361C>G	p.Asn787Lys	missense_variant	Exon 15 of 15	1		ENSP00000389270.2
ENSG00000249568	ENST00000508189.1	n.323G>C		non_coding_transcript_exon_variant	Exon 2 of 2	2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Mar 11, 2022

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.2391C>G (p.N797K) alteration is located in exon 16 (coding exon 15) of the FSTL5 gene. This alteration results from a C to G substitution at nucleotide position 2391, causing the asparagine (N) at amino acid position 797 to be replaced by a lysine (K). 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	0.65
BayesDel_addAF	Benign	-0.10	T
BayesDel_noAF	Benign	-0.39
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.085	T;.;.
Eigen	Uncertain	0.61
Eigen_PC	Uncertain	0.57
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Uncertain	0.93	D;D;D
M_CAP	Benign	0.017	T
MetaRNN	Uncertain	0.59	D;D;D
MetaSVM	Benign	-0.90	T
MutationAssessor	Uncertain	2.6	M;.;.
PrimateAI	Uncertain	0.61	T
PROVEAN	Uncertain	-3.8	D;D;D
REVEL	Benign	0.22
Sift	Uncertain	0.012	D;D;D
Sift4G	Uncertain	0.050	T;T;T
Polyphen		1.0	D;.;.
Vest4		0.56
MutPred		0.50		Gain of methylation at N797 (P = 0.004);.;.;
MVP		0.74
MPC		0.28
ClinPred		0.98	D
GERP RS		4.7
Varity_R		0.48
gMVP		0.71

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr4-162307052;