15-43632771-A-T

Variant names:

• chr15-43632771-A-T
• rs146674703
• NM_172095.4:c.1342T>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_172095.4(CATSPER2):​c.1342T>A​(p.Ser448Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000341 in 1,613,586 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000039 (0 hom., cov: 31)
  • Exomes 𝑓: 0.000034 (1 hom.)
• Consequence: CATSPER2 NM_172095.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.62
• Publications: 0 publications found

Genes affected

CATSPER2 (HGNC:18810): (cation channel sperm associated 2) This gene encodes a member of a family of cation channel proteins that localize to the flagellum of spermatozoa. Defects at this locus causes male infertility. Alternatively spliced transcript variants have been observed at this locus. Readthrough transcription originates upstream of this locus in diphosphoinositol pentakisphosphate kinase 1 pseudogene 1 and is represented by GeneID:110006325. Related pseudogenes are found next to this locus on chromosome 15 and on chromosome 5. [provided by RefSeq, Mar 2017]

PPIP5K1P1-CATSPER2 (HGNC:):

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.09462288).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_172095.4. 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
	CATSPER2	NM_172095.4	MANE Select	c.1342T>A	p.Ser448Thr	missense	Exon 11 of 13	NP_742093.1	Q96P56-1
	CATSPER2	NM_001282310.2		c.1354T>A	p.Ser452Thr	missense	Exon 11 of 13	NP_001269239.1	F8W9H2
	CATSPER2	NM_001282309.3		c.1336T>A	p.Ser446Thr	missense	Exon 12 of 14	NP_001269238.1	Q96P56-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CATSPER2	ENST00000396879.8	TSL:2 MANE Select	c.1342T>A	p.Ser448Thr	missense	Exon 11 of 13	ENSP00000380088.3	Q96P56-1
	CATSPER2	ENST00000381761.6	TSL:1	c.1354T>A	p.Ser452Thr	missense	Exon 11 of 13	ENSP00000371180.1	F8W9H2
	CATSPER2	ENST00000433380.5	TSL:1	n.1179-408T>A		intron	N/A	ENSP00000389746.1	Q96P56-3

Frequencies

GnomAD3 genomes AF: 0.0000395 AC: 6 AN: 151948 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000208

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000589

Gnomad OTH AF: 0.000478

GnomAD2 exomes AF: 0.0000676 AC: 17 AN: 251404 AF XY: 0.0000883

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000879

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000335 AC: 49 AN: 1461638 Hom.: 1 Cov.: 32 AF XY: 0.0000468 AC XY: 34 AN XY: 727108

African (AFR) AF: 0.00 AC: 0 AN: 33476

American (AMR) AF: 0.00 AC: 0 AN: 44716

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26128

East Asian (EAS) AF: 0.00 AC: 0 AN: 39680

South Asian (SAS) AF: 0.000302 AC: 26 AN: 86232

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53410

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

European-Non Finnish (NFE) AF: 0.0000189 AC: 21 AN: 1111844

Other (OTH) AF: 0.0000331 AC: 2 AN: 60384

GnomAD4 genome AF: 0.0000395 AC: 6 AN: 151948 Hom.: 0 Cov.: 31 AF XY: 0.0000674 AC XY: 5 AN XY: 74200

African (AFR) AF: 0.00 AC: 0 AN: 41366

American (AMR) AF: 0.00 AC: 0 AN: 15248

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3466

East Asian (EAS) AF: 0.00 AC: 0 AN: 5198

South Asian (SAS) AF: 0.000208 AC: 1 AN: 4806

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10584

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 314

European-Non Finnish (NFE) AF: 0.0000589 AC: 4 AN: 67964

Other (OTH) AF: 0.000478 AC: 1 AN: 2090

Alfa AF: 0.0000675 Hom.: 0

Bravo AF: 0.0000491

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000116 AC: 1

ExAC AF: 0.0000494 AC: 6

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	0.075
BayesDel_addAF	Benign	-0.21	T
BayesDel_noAF	Benign	-0.25
CADD	Benign	6.9
DANN	Benign	0.75
DEOGEN2	Benign	0.052	T
Eigen	Benign	-0.81
Eigen_PC	Benign	-0.84
FATHMM_MKL	Benign	0.23	N
LIST_S2	Benign	0.48	T
M_CAP	Benign	0.012	T
MetaRNN	Benign	0.095	T
MetaSVM	Uncertain	-0.080	T
MutationAssessor	Uncertain	2.2	M
PhyloP100		2.6
PrimateAI	Benign	0.36	T
PROVEAN	Benign	-0.57	N
REVEL	Benign	0.26
Sift	Benign	0.081	T
Sift4G	Benign	0.068	T
Polyphen		0.056	B
Vest4		0.15
MVP		0.71
MPC		0.20
ClinPred		0.20	T
GERP RS		2.7
Varity_R		0.14
gMVP		0.069
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: rs146674703; hg19: chr15-43924969;