chr19-5744490-C-T

Variant names:

• chr19-5744490-C-T
• rs540346018
• NM_152784.4:c.637C>T

Variant summary

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

The NM_152784.4(CATSPERD):​c.637C>T​(p.Leu213Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000616 in 1,460,014 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. L213V) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000062 (0 hom.)
• Consequence: CATSPERD NM_152784.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.99

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]

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
CATSPERD	NM_152784.4	c.637C>T	p.Leu213Phe	missense_variant	Exon 8 of 22	ENST00000381624.4	NP_689997.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CATSPERD	ENST00000381624.4	c.637C>T	p.Leu213Phe	missense_variant	Exon 8 of 22	1	NM_152784.4	ENSP00000371037.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000616 AC: 9 AN: 1460014 Hom.: 0 Cov.: 30 AF XY: 0.00000413 AC XY: 3 AN XY: 726302

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000810

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

TwinsUK AF: 0.000270 AC: 1

ALSPAC AF: 0.000259 AC: 1

EpiCase AF: 0.00

EpiControl AF: 0.0000593

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.47
BayesDel_addAF	Benign	-0.13	T
BayesDel_noAF	Benign	-0.42
CADD	Benign	21
DANN	Uncertain	1.0
DEOGEN2	Benign	0.028	T
Eigen	Benign	0.086
Eigen_PC	Benign	-0.11
FATHMM_MKL	Benign	0.46	N
LIST_S2	Benign	0.39	T
M_CAP	Benign	0.029	D
MetaRNN	Uncertain	0.71	D
MetaSVM	Benign	-0.81	T
MutationAssessor	Uncertain	2.1	M
PrimateAI	Benign	0.48	T
PROVEAN	Uncertain	-3.0	D
REVEL	Benign	0.15
Sift	Uncertain	0.017	D
Sift4G	Pathogenic	0.0	D
Polyphen		1.0	D
Vest4		0.58
MVP		0.38
MPC		0.70
ClinPred		0.76	D
GERP RS		2.6
Varity_R		0.20
gMVP		0.64

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: rs540346018; hg19: chr19-5744501;