11-64300859-A-T

Position:

• chr11-64300859-A-T

Variant summary

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

The NM_001039496.2(CATSPERZ):​c.224A>T​(p.Glu75Val) 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. 14/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: CATSPERZ NM_001039496.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.153

Genes affected

CATSPERZ (HGNC:19231): (catsper channel auxiliary subunit zeta) Predicted to be involved in flagellated sperm motility; male meiotic nuclear division; and sperm capacitation. Located in cytoplasm and sperm principal piece. [provided by Alliance of Genome Resources, Apr 2022]

KCNK4-CATSPERZ (HGNC:):

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=0.07471782).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CATSPERZ	NM_001039496.2	c.224A>T	p.Glu75Val	missense_variant	2/5	ENST00000328404.8	NP_001034585.1
KCNK4-CATSPERZ	NR_133662.1	n.2231A>T		non_coding_transcript_exon_variant	8/11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CATSPERZ	ENST00000328404.8	c.224A>T	p.Glu75Val	missense_variant	2/5	1	NM_001039496.2	ENSP00000491717	P2
CATSPERZ	ENST00000539943.1	c.98A>T	p.Glu33Val	missense_variant	1/4	2		ENSP00000443917	A2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jun 10, 2024

The c.224A>T (p.E75V) alteration is located in exon 2 (coding exon 2) of the TEX40 gene. This alteration results from a A to T substitution at nucleotide position 224, causing the glutamic acid (E) at amino acid position 75 to be replaced by a valine (V). 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	0.18
BayesDel_addAF	Benign	-0.22	T
BayesDel_noAF	Benign	-0.56
CADD	Benign	6.0
DANN	Uncertain	0.98
DEOGEN2	Benign	0.066	T;.
Eigen	Benign	-0.91
Eigen_PC	Benign	-1.0
FATHMM_MKL	Benign	0.012	N
LIST_S2	Benign	0.35	T;T
M_CAP	Benign	0.015	T
MetaRNN	Benign	0.075	T;T
MetaSVM	Benign	-1.0	T
MutationTaster	Benign	1.0	N;N
PrimateAI	Benign	0.24	T
PROVEAN	Benign	-1.5	.;N
REVEL	Benign	0.026
Sift	Benign	0.061	.;T
Sift4G	Uncertain	0.046	.;D
Polyphen		0.44	B;.
Vest4		0.11
MutPred		0.33		Loss of solvent accessibility (P = 0.0013);.;
MVP		0.055
MPC		0.68
ClinPred		0.13	T
GERP RS		0.52
Varity_R		0.075
gMVP		0.061

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: rs2034912469; hg19: chr11-64068331;