NM_024764.4:c.2729A>C

Variant names:

• chr14-91591983-T-G
• rs1893413804
• NM_024764.4:c.2729A>C

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2 PP3

The NM_024764.4(CATSPERB):​c.2729A>C​(p.Gln910Pro) variant causes a missense change. The variant allele was found at a frequency of 0.00000274 in 1,461,132 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic 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. Q910R) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000027 (0 hom.)
• Consequence: CATSPERB NM_024764.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.60
• Publications: 0 publications found

Genes affected

CATSPERB (HGNC:20500): (cation channel sperm associated auxiliary subunit beta) Predicted to be involved in cell differentiation and spermatogenesis. Predicted to be located in plasma membrane. Predicted to be part of CatSper complex. Predicted to be active in cilium. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Uncertain_significance. The variant received 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.777

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_024764.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CATSPERB	NM_024764.4	MANE Select	c.2729A>C	p.Gln910Pro	missense	Exon 23 of 27	NP_079040.2	Q9H7T0-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CATSPERB	ENST00000256343.8	TSL:1 MANE Select	c.2729A>C	p.Gln910Pro	missense	Exon 23 of 27	ENSP00000256343.3	Q9H7T0-1
	CATSPERB	ENST00000556429.1	TSL:3	n.570A>C		non_coding_transcript_exon	Exon 1 of 2
	CATSPERB	ENST00000557036.1	TSL:2	n.*1210A>C		non_coding_transcript_exon	Exon 9 of 13	ENSP00000451083.1	H0YJA5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000274 AC: 4 AN: 1461132 Hom.: 0 Cov.: 30 AF XY: 0.00000413 AC XY: 3 AN XY: 726918

African (AFR) AF: 0.00 AC: 0 AN: 33468

American (AMR) AF: 0.00 AC: 0 AN: 44652

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26124

East Asian (EAS) AF: 0.00 AC: 0 AN: 39672

South Asian (SAS) AF: 0.00 AC: 0 AN: 86180

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53418

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5766

European-Non Finnish (NFE) AF: 0.00000360 AC: 4 AN: 1111474

Other (OTH) AF: 0.00 AC: 0 AN: 60378

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.57
BayesDel_addAF	Uncertain	0.049	T
BayesDel_noAF	Benign	-0.17
CADD	Uncertain	25
DANN	Uncertain	0.99
DEOGEN2	Benign	0.25	T
Eigen	Uncertain	0.59
Eigen_PC	Uncertain	0.57
FATHMM_MKL	Uncertain	0.84	D
M_CAP	Benign	0.044	D
MetaRNN	Pathogenic	0.78	D
MetaSVM	Benign	-0.37	T
MutationAssessor	Uncertain	2.8	M
PhyloP100		3.6
PrimateAI	Benign	0.42	T
PROVEAN	Uncertain	-4.3	D
REVEL	Benign	0.18
Sift	Uncertain	0.0090	D
Sift4G	Pathogenic	0.0	D
Polyphen		1.0	D
Vest4		0.74
MutPred		0.29		Gain of catalytic residue at K909 (P = 0)
MVP		0.74
MPC		0.89
ClinPred		1.0	D
GERP RS		5.3
Varity_R		0.80
gMVP		0.79
Mutation Taster		=92/8	polymorphism

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

Other links and lift over

dbSNP: rs1893413804; hg19: chr14-92058327;