NM_080610.3:c.127A>G

Variant names:

• chr20-23568324-T-C
• NM_080610.3:c.127A>G

Variant summary

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

The NM_080610.3(CST9L):​c.127A>G​(p.Met43Val) 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. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: CST9L NM_080610.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.996
• Publications: 0 publications found

Genes affected

CST9L (HGNC:16233): (cystatin 9 like) The cystatin superfamily encompasses proteins that contain multiple cystatin-like sequences. Some of the members are active cysteine protease inhibitors, while others have lost or perhaps never acquired this inhibitory activity. There are three inhibitory families in the superfamily, including the type 1 cystatins (stefins), type 2 cystatins and the kininogens. The type 2 cystatin proteins are a class of cysteine proteinase inhibitors found in a variety of human fluids and secretions. The cystatin locus on chromosome 20 contains the majority of the type 2 cystatin genes and pseudogenes. This gene is located in the cystatin locus and encodes a protein similar to mouse cystatin 9. Based on its testis-specific expression, it is likely to have a role in tissue reorganization during early testis development. [provided by RefSeq, Jul 2008]

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=0.08576155).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_080610.3. 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
	CST9L	NM_080610.3	MANE Select	c.127A>G	p.Met43Val	missense	Exon 1 of 3	NP_542177.1	A0A140VJH1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CST9L	ENST00000376979.4	TSL:1 MANE Select	c.127A>G	p.Met43Val	missense	Exon 1 of 3	ENSP00000366178.3	Q9H4G1

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	Benign	0.11
BayesDel_addAF	Benign	-0.38	T
BayesDel_noAF	Benign	-0.78
CADD	Benign	0.18
DANN	Benign	0.66
DEOGEN2	Benign	0.050	T
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.025	N
LIST_S2	Benign	0.33	T
M_CAP	Benign	0.0016	T
MetaRNN	Benign	0.086	T
MetaSVM	Benign	-0.97	T
MutationAssessor	Benign	1.1	L
PhyloP100		-1.0
PrimateAI	Benign	0.31	T
PROVEAN	Benign	-0.63	N
REVEL	Benign	0.010
Sift	Benign	0.19	T
Sift4G	Benign	0.23	T
Polyphen		0.10	B
Vest4		0.081
MutPred		0.42		Loss of catalytic residue at M43 (P = 0.0429)
MVP		0.27
MPC		0.023
ClinPred		0.041	T
GERP RS		-1.2
PromoterAI		-0.027	Neutral
Varity_R		0.057
gMVP		0.16
Mutation Taster		=98/2	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: chr20-23548961;