rs754044973

Variant names:

• chr14-91610547-G-A
• rs754044973
• NM_024764.4:c.2531C>T

Your query was ambiguous. Multiple possible variants found:

• chr14-91610547-G-A
• chr14-91610547-G-C

Variant summary

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

The NM_024764.4(CATSPERB):​c.2531C>T​(p.Pro844Leu) 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. 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. P844R) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: CATSPERB NM_024764.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.39

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

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=0.2275761).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CATSPERB	NM_024764.4	c.2531C>T	p.Pro844Leu	missense_variant	Exon 21 of 27	ENST00000256343.8	NP_079040.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CATSPERB	ENST00000256343.8	c.2531C>T	p.Pro844Leu	missense_variant	Exon 21 of 27	1	NM_024764.4	ENSP00000256343.3
CATSPERB	ENST00000557036.1	n.*1012C>T		non_coding_transcript_exon_variant	Exon 7 of 13	2		ENSP00000451083.1
CATSPERB	ENST00000557036.1	n.*1012C>T		3_prime_UTR_variant	Exon 7 of 13	2		ENSP00000451083.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.16
BayesDel_addAF	Benign	-0.16	T
BayesDel_noAF	Benign	-0.47
CADD	Uncertain	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.24	T
Eigen	Benign	-0.016
Eigen_PC	Benign	-0.090
FATHMM_MKL	Benign	0.32	N
M_CAP	Benign	0.031	D
MetaRNN	Benign	0.23	T
MetaSVM	Benign	-0.94	T
MutationAssessor	Uncertain	2.5	M
PrimateAI	Benign	0.35	T
PROVEAN	Pathogenic	-5.4	D
REVEL	Benign	0.12
Sift	Benign	0.032	D
Sift4G	Uncertain	0.031	D
Polyphen		0.78	P
Vest4		0.23
MutPred		0.51		Gain of catalytic residue at K841 (P = 0);
MVP		0.49
MPC		0.49
ClinPred		0.95	D
GERP RS		3.7
Varity_R		0.10
gMVP		0.43

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

LitVar

Other links and lift over

dbSNP: rs754044973; hg19: chr14-92076891;