chr11-64300814-G-C

Position:

• chr11-64300814-G-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.179G>C​(p.Ser60Thr) 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 33)
• Consequence: CATSPERZ NM_001039496.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.0800

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-TEX40 (HGNC:56753): (KCNK4-CATSPERZ readthrough (NMD candidate)) This locus represents naturally occurring readthrough transcription between the neighboring KCNK4 (potassium channel subfamily K member 4) and the downstream TEX40 (testis expressed 40) chromosome 11. The readthrough transcript is a candidate for nonsense-mediated mRNA decay (NMD), and is unlikely to produce a protein product. [provided by RefSeq, Nov 2015]

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=0.07720128).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CATSPERZ	NM_001039496.2	c.179G>C	p.Ser60Thr	missense_variant	2/5	ENST00000328404.8	NP_001034585.1
KCNK4-CATSPERZ	NR_133662.1	n.2186G>C		non_coding_transcript_exon_variant	8/11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CATSPERZ	ENST00000328404.8	c.179G>C	p.Ser60Thr	missense_variant	2/5	1	NM_001039496.2	ENSP00000491717.1
KCNK4-TEX40	ENST00000539086.5	n.2186G>C		non_coding_transcript_exon_variant	8/11	1
CATSPERZ	ENST00000539943.1	c.53G>C	p.Ser18Thr	missense_variant	1/4	2		ENSP00000443917.1

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

Sep 10, 2024

The c.179G>C (p.S60T) alteration is located in exon 2 (coding exon 2) of the TEX40 gene. This alteration results from a G to C substitution at nucleotide position 179, causing the serine (S) at amino acid position 60 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	0.11
BayesDel_addAF	Benign	-0.36	T
BayesDel_noAF	Benign	-0.75
CADD	Benign	0.39
DANN	Benign	0.37
DEOGEN2	Benign	0.011	T;.
Eigen	Benign	-0.82
Eigen_PC	Benign	-0.92
FATHMM_MKL	Benign	0.069	N
LIST_S2	Benign	0.27	T;T
M_CAP	Benign	0.0054	T
MetaRNN	Benign	0.077	T;T
MetaSVM	Benign	-1.1	T
PrimateAI	Benign	0.30	T
PROVEAN	Benign	-0.75	.;N
REVEL	Benign	0.15
Sift	Benign	0.53	.;T
Sift4G	Benign	0.61	.;T
Polyphen		0.88	P;.
Vest4		0.059
MutPred		0.10		Loss of MoRF binding (P = 0.1135);.;
MVP		0.048
MPC		0.45
ClinPred		0.15	T
GERP RS		2.2
Varity_R		0.049
gMVP		0.026

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: chr11-64068286;