14-91610551-T-C

Variant names:

• chr14-91610551-T-C
• rs775203748
• NM_024764.4:c.2527A>G

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_024764.4(CATSPERB):​c.2527A>G​(p.Ile843Val) variant causes a missense change. The variant allele was found at a frequency of 0.00000274 in 1,461,832 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 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. I843F) 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: 3.95
• 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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.26953933).

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.2527A>G	p.Ile843Val	missense	Exon 21 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.2527A>G	p.Ile843Val	missense	Exon 21 of 27	ENSP00000256343.3	Q9H7T0-1
	CATSPERB	ENST00000557036.1	TSL:2	n.*1008A>G		non_coding_transcript_exon	Exon 7 of 13	ENSP00000451083.1	H0YJA5
	CATSPERB	ENST00000557036.1	TSL:2	n.*1008A>G		3_prime_UTR	Exon 7 of 13	ENSP00000451083.1	H0YJA5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000274 AC: 4 AN: 1461832 Hom.: 0 Cov.: 33 AF XY: 0.00000413 AC XY: 3 AN XY: 727216

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26134

East Asian (EAS) AF: 0.0000504 AC: 2 AN: 39696

South Asian (SAS) AF: 0.00 AC: 0 AN: 86256

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53378

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.00000180 AC: 2 AN: 1112002

Other (OTH) AF: 0.00 AC: 0 AN: 60396

GnomAD4 genome Cov.: 32

TwinsUK AF: 0.000270 AC: 1

ALSPAC AF: 0.00 AC: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.21
BayesDel_addAF	Benign	-0.18	T
BayesDel_noAF	Benign	-0.49
CADD	Benign	21
DANN	Benign	0.92
DEOGEN2	Benign	0.057	T
Eigen	Benign	0.10
Eigen_PC	Benign	0.0019
FATHMM_MKL	Benign	0.74	D
M_CAP	Benign	0.020	T
MetaRNN	Benign	0.27	T
MetaSVM	Benign	-0.93	T
MutationAssessor	Uncertain	2.8	M
PhyloP100		3.9
PrimateAI	Uncertain	0.51	T
PROVEAN	Benign	-0.53	N
REVEL	Benign	0.11
Sift	Benign	0.25	T
Sift4G	Benign	0.12	T
Polyphen		0.97	D
Vest4		0.20
MutPred		0.30		Gain of catalytic residue at K841 (P = 0)
MVP		0.35
MPC		0.42
ClinPred		0.74	D
GERP RS		4.6
Varity_R		0.050
gMVP		0.21
Mutation Taster		=97/3	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: rs775203748; hg19: chr14-92076895;