rs755439239

Variant names:

• chr18-24155973-C-T
• rs755439239
• NM_153769.3:c.472C>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_153769.3(CABYR):​c.472C>T​(p.Pro158Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000889 in 1,461,890 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000089 (1 hom.)
• Consequence: CABYR NM_153769.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.20
• Publications: 1 publications found

Genes affected

CABYR (HGNC:15569): (calcium binding tyrosine phosphorylation regulated) To reach fertilization competence, spermatozoa undergo a series of morphological and molecular maturational processes, termed capacitation, involving protein tyrosine phosphorylation and increased intracellular calcium. The protein encoded by this gene localizes to the principal piece of the sperm flagellum in association with the fibrous sheath and exhibits calcium-binding when phosphorylated during capacitation. A pseudogene on chromosome 3 has been identified for this gene. Alternatively spliced transcript variants encoding distinct protein isoforms have been found for this gene. [provided by RefSeq, Jul 2013]

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.23536849).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_153769.3. 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
	CABYR	NM_153769.3	MANE Select	c.472C>T	p.Pro158Ser	missense	Exon 4 of 6	NP_722453.1	O75952-3
	CABYR	NM_012189.4		c.472C>T	p.Pro158Ser	missense	Exon 4 of 6	NP_036321.2
	CABYR	NM_153768.3		c.418C>T	p.Pro140Ser	missense	Exon 3 of 5	NP_722452.1	O75952-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CABYR	ENST00000399496.8	TSL:1 MANE Select	c.472C>T	p.Pro158Ser	missense	Exon 4 of 6	ENSP00000382419.3	O75952-3
	CABYR	ENST00000621648.4	TSL:1	c.472C>T	p.Pro158Ser	missense	Exon 4 of 6	ENSP00000483621.1	O75952-1
	CABYR	ENST00000399481.6	TSL:1	c.418C>T	p.Pro140Ser	missense	Exon 3 of 5	ENSP00000382404.3	O75952-2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.0000398 AC: 10 AN: 251350 AF XY: 0.0000368

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000202

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000176

Gnomad OTH exome AF: 0.000163

GnomAD4 exome AF: 0.00000889 AC: 13 AN: 1461890 Hom.: 1 Cov.: 32 AF XY: 0.0000110 AC XY: 8 AN XY: 727246

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

American (AMR) AF: 0.000157 AC: 7 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53420

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

European-Non Finnish (NFE) AF: 0.00000270 AC: 3 AN: 1112008

Other (OTH) AF: 0.0000497 AC: 3 AN: 60396

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000151

ExAC AF: 0.0000330 AC: 4

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.092
BayesDel_addAF	Benign	-0.26	T
BayesDel_noAF	Benign	-0.32
CADD	Benign	18
DANN	Uncertain	1.0
DEOGEN2	Benign	0.13	T
Eigen	Benign	0.19
Eigen_PC	Benign	0.078
FATHMM_MKL	Benign	0.39	N
LIST_S2	Uncertain	0.91	D
M_CAP	Uncertain	0.11	D
MetaRNN	Benign	0.24	T
MetaSVM	Uncertain	-0.083	T
MutationAssessor	Benign	1.8	L
PhyloP100		2.2
PrimateAI	Benign	0.36	T
PROVEAN	Uncertain	-2.5	D
REVEL	Benign	0.16
Sift	Uncertain	0.0080	D
Sift4G	Pathogenic	0.0	D
Polyphen		1.0	D
Vest4		0.23
MutPred		0.39		Gain of relative solvent accessibility (P = 0.005)
MVP		0.60
MPC		0.50
ClinPred		0.36	T
GERP RS		5.1
PromoterAI		-0.0098	Neutral
Varity_R		0.10
gMVP		0.21
Mutation Taster		=84/16	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: rs755439239; hg19: chr18-21735937;