19-5720748-T-C

Variant names:

• chr19-5720748-T-C
• rs2055440287
• NM_152784.4:c.11T>C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_152784.4(CATSPERD):​c.11T>C​(p.Leu4Ser) 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. 15/21 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: CATSPERD NM_152784.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.327

Genes affected

CATSPERD (HGNC:28598): (cation channel sperm associated auxiliary subunit delta) Predicted to be involved in flagellated sperm motility and sperm capacitation. Predicted to be located in sperm principal piece. Predicted to be part of CatSper complex. [provided by Alliance of Genome Resources, Apr 2022]

LONP1 (HGNC:9479): (lon peptidase 1, mitochondrial) This gene encodes a mitochondrial matrix protein that belongs to the Lon family of ATP-dependent proteases. This protein mediates the selective degradation of misfolded, unassembled or oxidatively damaged polypeptides in the mitochondrial matrix. It may also have a chaperone function in the assembly of inner membrane protein complexes, and participate in the regulation of mitochondrial gene expression and maintenance of the integrity of the mitochondrial genome. Decreased expression of this gene has been noted in a patient with hereditary spastic paraplegia (PMID:18378094). Alternatively spliced transcript variants have been found for this gene. [provided by RefSeq, Feb 2013]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.20672873).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CATSPERD	NM_152784.4	c.11T>C	p.Leu4Ser	missense_variant	Exon 1 of 22	ENST00000381624.4	NP_689997.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CATSPERD	ENST00000381624.4	c.11T>C	p.Leu4Ser	missense_variant	Exon 1 of 22	1	NM_152784.4	ENSP00000371037.3
LONP1	ENST00000540670.6	c.-689A>G		upstream_gene_variant		2		ENSP00000441523.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Jun 19, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.11T>C (p.L4S) alteration is located in exon 1 (coding exon 1) of the CATSPERD gene. This alteration results from a T to C substitution at nucleotide position 11, causing the leucine (L) at amino acid position 4 to be replaced by a serine (S). 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	Benign	0.24
BayesDel_addAF	Benign	-0.020	T
BayesDel_noAF	Benign	-0.27
CADD	Benign	7.3
DANN	Benign	0.91
DEOGEN2	Benign	0.0056	T
Eigen	Benign	-0.31
Eigen_PC	Benign	-0.57
FATHMM_MKL	Benign	0.36	N
LIST_S2	Benign	0.33	T
M_CAP	Benign	0.0061	T
MetaRNN	Benign	0.21	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.4	L
PrimateAI	Benign	0.36	T
PROVEAN	Benign	-1.3	N
REVEL	Benign	0.12
Sift	Uncertain	0.0010	D
Sift4G	Uncertain	0.0020	D
Polyphen		0.99	D
Vest4		0.20
MutPred		0.53		Gain of disorder (P = 0.0083);
MVP		0.39
MPC		0.22
ClinPred		0.25	T
GERP RS		1.2
Varity_R		0.22
gMVP		0.61

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: rs2055440287; hg19: chr19-5720759;