NM_020116.5:c.1978T>C

Variant names:

• chr4-161386313-A-G
• NM_020116.5:c.1978T>C

Variant summary

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

The NM_020116.5(FSTL5):​c.1978T>C​(p.Tyr660His) variant causes a missense change involving the alteration of a conserved nucleotide. 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: 8.82
• Publications: 0 publications found

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

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_020116.5. 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
	FSTL5	NM_020116.5	MANE Select	c.1978T>C	p.Tyr660His	missense	Exon 16 of 16	NP_064501.2	Q8N475-1
	FSTL5	NM_001128427.3		c.1975T>C	p.Tyr659His	missense	Exon 16 of 16	NP_001121899.1	Q8N475-2
	FSTL5	NM_001128428.3		c.1948T>C	p.Tyr650His	missense	Exon 15 of 15	NP_001121900.1	Q8N475-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FSTL5	ENST00000306100.10	TSL:1 MANE Select	c.1978T>C	p.Tyr660His	missense	Exon 16 of 16	ENSP00000305334.4	Q8N475-1
	FSTL5	ENST00000379164.8	TSL:1	c.1975T>C	p.Tyr659His	missense	Exon 16 of 16	ENSP00000368462.4	Q8N475-2
	FSTL5	ENST00000427802.2	TSL:1	c.1948T>C	p.Tyr650His	missense	Exon 15 of 15	ENSP00000389270.2	Q8N475-3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.35
BayesDel_addAF	Benign	-0.0011	T
BayesDel_noAF	Benign	-0.24
CADD	Benign	22
DANN	Uncertain	1.0
DEOGEN2	Benign	0.091	T
Eigen	Uncertain	0.67
Eigen_PC	Uncertain	0.62
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Pathogenic	0.99	D
M_CAP	Benign	0.020	T
MetaRNN	Uncertain	0.49	T
MetaSVM	Benign	-0.81	T
MutationAssessor	Pathogenic	2.9	M
PhyloP100		8.8
PrimateAI	Uncertain	0.61	T
PROVEAN	Uncertain	-4.3	D
REVEL	Uncertain	0.32
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0	D
Polyphen		0.98	D
Vest4		0.48
MutPred		0.59		Gain of sheet (P = 0.0827)
MVP		0.54
MPC		0.39
ClinPred		1.0	D
GERP RS		4.4
Varity_R		0.74
gMVP		0.66
Mutation Taster		=88/12	polymorphism

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

Other links and lift over

hg19: chr4-162307465;