1-244479720-G-A

Variant names:

• chr1-244479720-G-A
• rs933138054
• NM_001130957.2:c.262G>A

Variant summary

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

The NM_001130957.2(CATSPERE):​c.262G>A​(p.Glu88Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000153 in 1,440,060 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.000015 (0 hom.)
• Consequence: CATSPERE NM_001130957.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.28

Genes affected

CATSPERE (HGNC:28491): (catsper channel auxiliary subunit epsilon) Located in sperm principal piece. [provided by Alliance of Genome Resources, Apr 2022]

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=0.1862602).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CATSPERE	NM_001130957.2	c.262G>A	p.Glu88Lys	missense_variant	Exon 5 of 22	ENST00000366534.9	NP_001124429.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CATSPERE	ENST00000366534.9	c.262G>A	p.Glu88Lys	missense_variant	Exon 5 of 22	2	NM_001130957.2	ENSP00000355492.4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.0000153 AC: 22 AN: 1440060 Hom.: 0 Cov.: 26 AF XY: 0.0000167 AC XY: 12 AN XY: 717222

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: 0.0000201

Gnomad4 OTH exome AF: 0.00

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

Aug 09, 2021

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.262G>A (p.E88K) alteration is located in exon 5 (coding exon 5) of the C1orf101 gene. This alteration results from a G to A substitution at nucleotide position 262, causing the glutamic acid (E) at amino acid position 88 to be replaced by a lysine (K). 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	0.14
BayesDel_addAF	Benign	-0.094	T
BayesDel_noAF	Benign	-0.37
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Benign	0.015	T;.;.
Eigen	Uncertain	0.37
Eigen_PC	Uncertain	0.32
FATHMM_MKL	Uncertain	0.76	D
LIST_S2	Benign	0.63	T;T;T
M_CAP	Benign	0.0089	T
MetaRNN	Benign	0.19	T;T;T
MetaSVM	Benign	-0.99	T
PROVEAN	Benign	-1.1	N;N;N
REVEL	Benign	0.13
Sift	Benign	0.080	T;T;T
Sift4G	Benign	0.092	T;D;T
Polyphen		0.95	P;D;P
Vest4		0.45
MutPred		0.37		Gain of ubiquitination at E88 (P = 0.0104);Gain of ubiquitination at E88 (P = 0.0104);.;
MVP		0.23
MPC		0.64
ClinPred		0.87	D
GERP RS		3.4
Varity_R		0.12
gMVP		0.44

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs933138054; hg19: chr1-244643022;