4-161385752-C-T

Variant names:

• chr4-161385752-C-T
• rs1473277955
• NM_020116.5:c.2539G>A

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_020116.5(FSTL5):​c.2539G>A​(p.Ala847Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000014 in 1,425,648 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: FSTL5 NM_020116.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.55
• 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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.22885457).

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.2539G>A	p.Ala847Thr	missense	Exon 16 of 16	NP_064501.2	Q8N475-1
	FSTL5	NM_001128427.3		c.2536G>A	p.Ala846Thr	missense	Exon 16 of 16	NP_001121899.1	Q8N475-2
	FSTL5	NM_001128428.3		c.2509G>A	p.Ala837Thr	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.2539G>A	p.Ala847Thr	missense	Exon 16 of 16	ENSP00000305334.4	Q8N475-1
	FSTL5	ENST00000379164.8	TSL:1	c.2536G>A	p.Ala846Thr	missense	Exon 16 of 16	ENSP00000368462.4	Q8N475-2
	FSTL5	ENST00000427802.2	TSL:1	c.2509G>A	p.Ala837Thr	missense	Exon 15 of 15	ENSP00000389270.2	Q8N475-3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000140 AC: 2 AN: 1425648 Hom.: 0 Cov.: 28 AF XY: 0.00000141 AC XY: 1 AN XY: 708224

African (AFR) AF: 0.00 AC: 0 AN: 32022

American (AMR) AF: 0.00 AC: 0 AN: 38902

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 23822

East Asian (EAS) AF: 0.00 AC: 0 AN: 39478

South Asian (SAS) AF: 0.00 AC: 0 AN: 80536

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52400

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5572

European-Non Finnish (NFE) AF: 0.00000183 AC: 2 AN: 1094100

Other (OTH) AF: 0.00 AC: 0 AN: 58816

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	Benign	0.088
BayesDel_addAF	Uncertain	0.033	T
BayesDel_noAF	Benign	-0.19
CADD	Benign	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.0066	T
Eigen	Uncertain	0.36
Eigen_PC	Uncertain	0.48
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.96	D
M_CAP	Benign	0.016	T
MetaRNN	Benign	0.23	T
MetaSVM	Benign	-0.44	T
MutationAssessor	Uncertain	2.0	M
PhyloP100		3.5
PrimateAI	Uncertain	0.53	T
PROVEAN	Benign	-0.65	N
REVEL	Benign	0.18
Sift	Uncertain	0.013	D
Sift4G	Uncertain	0.019	D
Polyphen		0.91	P
Vest4		0.32
MutPred		0.30		Loss of sheet (P = 0.0037)
MVP		0.75
MPC		0.35
ClinPred		0.94	D
GERP RS		5.8
Varity_R		0.13
gMVP		0.52
Mutation Taster		=89/11	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

dbSNP: rs1473277955; hg19: chr4-162306904;