chr4-70335931-T-A

Variant names:

• chr4-70335931-T-A
• rs2291182
• NM_033122.4:c.892T>A

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_033122.4(CABS1):​c.892T>A​(p.Trp298Arg) 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 pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: CABS1 NM_033122.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.31
• Publications: 16 publications found

Genes affected

CABS1 (HGNC:30710): (calcium binding protein, spermatid associated 1) Predicted to enable calcium ion binding activity. Predicted to be involved in flagellated sperm motility and spermatogenesis. Predicted to be located in acrosomal vesicle and sperm principal piece. Predicted to be active in mitochondrial inner membrane and motile cilium. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Uncertain_significance. The variant received 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.926

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CABS1	NM_033122.4	c.892T>A	p.Trp298Arg	missense_variant	Exon 1 of 2	ENST00000273936.6	NP_149113.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CABS1	ENST00000273936.6	c.892T>A	p.Trp298Arg	missense_variant	Exon 1 of 2	1	NM_033122.4	ENSP00000273936.4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 37

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.77
BayesDel_addAF	Uncertain	0.074	D
BayesDel_noAF	Benign	-0.13
CADD	Benign	23
DANN	Uncertain	0.99
DEOGEN2	Benign	0.054	T
Eigen	Uncertain	0.32
Eigen_PC	Uncertain	0.26
FATHMM_MKL	Uncertain	0.90	D
LIST_S2	Benign	0.27	T
M_CAP	Benign	0.030	D
MetaRNN	Pathogenic	0.93	D
MetaSVM	Benign	-0.69	T
MutationAssessor	Benign	1.0	L
PhyloP100		3.3
PrimateAI	Uncertain	0.52	T
PROVEAN	Pathogenic	-13	D
REVEL	Uncertain	0.32
Sift	Uncertain	0.0060	D
Sift4G	Benign	0.50	T
Polyphen		1.0	D
Vest4		0.77
MutPred		0.55		Gain of disorder (P = 0.012);
MVP		0.63
MPC		0.38
ClinPred		1.0	D
GERP RS		4.8
Varity_R		0.37
gMVP		0.0076
Mutation Taster		=86/14	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: rs2291182; hg19: chr4-71201648;