11-64300667-A-C

Position:

• chr11-64300667-A-C

Variant summary

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

The NM_001039496.2(CATSPERZ):​c.32A>C​(p.Lys11Thr) 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. 11/16 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: -0.0390

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=0.111233026).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CATSPERZ	NM_001039496.2	c.32A>C	p.Lys11Thr	missense_variant	2/5	ENST00000328404.8
KCNK4-CATSPERZ	NR_133662.1	n.2039A>C		non_coding_transcript_exon_variant	8/11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CATSPERZ	ENST00000328404.8	c.32A>C	p.Lys11Thr	missense_variant	2/5	1	NM_001039496.2	P2
CATSPERZ	ENST00000539943.1	c.-95A>C		5_prime_UTR_variant	1/4	2		A2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

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

Aug 09, 2021

The c.32A>C (p.K11T) alteration is located in exon 2 (coding exon 2) of the TEX40 gene. This alteration results from a A to C substitution at nucleotide position 32, causing the lysine (K) at amino acid position 11 to be replaced by a threonine (T). 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	0.13
BayesDel_noAF	Benign	-0.66
CADD	Benign	16
DANN	Uncertain	0.99
DEOGEN2	Benign	0.056	T
Eigen	Benign	-0.83
Eigen_PC	Benign	-0.95
FATHMM_MKL	Benign	0.027	N
LIST_S2	Benign	0.44	T
M_CAP	Benign	0.0034	T
MetaRNN	Benign	0.11	T
MetaSVM	Benign	-1.0	T
MutationTaster	Benign	1.0	N;N
PrimateAI	Benign	0.32	T
REVEL	Benign	0.038
Polyphen		0.89	P
MutPred		0.19		Loss of ubiquitination at K11 (P = 0.0056);
MPC		0.71
GERP RS		1.3
Varity_R		0.063
gMVP		0.039

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr11-64068139;