1-244572425-A-G

Variant names:

• chr1-244572425-A-G
• NM_001130957.2:c.1603A>G

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 4P and 2B. PM1 PM2 BP4_Moderate

The NM_001130957.2(CATSPERE):​c.1603A>G​(p.Asn535Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000688 in 1,454,536 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 11/19 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. N535H) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: CATSPERE NM_001130957.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.725

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 2 ACMG points.

• PM1: In a glycosylation_site N-linked (GlcNAc...) asparagine (size 0) in uniprot entity CTSRE_HUMAN
• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.10608819).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CATSPERE	NM_001130957.2	c.1603A>G	p.Asn535Asp	missense_variant	Exon 11 of 22	ENST00000366534.9	NP_001124429.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CATSPERE	ENST00000366534.9	c.1603A>G	p.Asn535Asp	missense_variant	Exon 11 of 22	2	NM_001130957.2	ENSP00000355492.4

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.88e-7 AC: 1 AN: 1454536 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 724064

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: 0.00

Gnomad4 OTH exome AF: 0.0000166

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.31	T
BayesDel_noAF	Benign	-0.68
CADD	Benign	11
DANN	Uncertain	0.98
DEOGEN2	Benign	0.022	.;T;.;.
Eigen	Benign	-0.65
Eigen_PC	Benign	-0.72
FATHMM_MKL	Benign	0.054	N
LIST_S2	Benign	0.66	T;T;T;T
M_CAP	Benign	0.0073	T
MetaRNN	Benign	0.11	T;T;T;T
MetaSVM	Benign	-1.1	T
PROVEAN	Uncertain	-2.5	N;N;N;D
REVEL	Benign	0.065
Sift	Benign	0.087	T;T;D;T
Sift4G	Benign	0.19	T;T;T;T
Polyphen		0.79, 0.25	.;P;P;B
Vest4		0.11
MutPred		0.38		.;Loss of helix (P = 0.079);Loss of helix (P = 0.079);.;
MVP		0.15
MPC		0.30
ClinPred		0.19	T
GERP RS		4.1
Varity_R		0.10
gMVP		0.40

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: chr1-244735727;