NM_198559.2:c.490C>T

Variant names:

• chr2-218362762-C-T
• rs1028839934
• NM_198559.2:c.490C>T

Variant summary

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

The NM_198559.2(CATIP):​c.490C>T​(p.Pro164Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,854 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/20 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. P164T) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: CATIP NM_198559.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.01
• Publications: 0 publications found

Genes affected

CATIP (HGNC:25062): (ciliogenesis associated TTC17 interacting protein) Involved in actin filament polymerization and cilium organization. Located in several cellular components, including actin cytoskeleton; nucleus; and plasma membrane. Implicated in spermatogenic failure. [provided by Alliance of Genome Resources, Apr 2022]

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=0.08634913).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_198559.2. 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
	CATIP	NM_198559.2	MANE Select	c.490C>T	p.Pro164Ser	missense	Exon 6 of 10	NP_940961.1	Q7Z7H3
	CATIP	NM_001320865.2		c.523C>T	p.Pro175Ser	missense	Exon 6 of 10	NP_001307794.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CATIP	ENST00000289388.4	TSL:1 MANE Select	c.490C>T	p.Pro164Ser	missense	Exon 6 of 10	ENSP00000289388.3	Q7Z7H3
	CATIP	ENST00000851696.1		c.523C>T	p.Pro175Ser	missense	Exon 6 of 10	ENSP00000521755.1
	CATIP	ENST00000851694.1		c.397C>T	p.Pro133Ser	missense	Exon 5 of 9	ENSP00000521753.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00000398 AC: 1 AN: 251376 AF XY: 0.00

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: 0.00000880

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1461854 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 727234

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

American (AMR) AF: 0.00 AC: 0 AN: 44720

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 39698

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

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53408

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5766

European-Non Finnish (NFE) AF: 8.99e-7 AC: 1 AN: 1111994

Other (OTH) AF: 0.0000166 AC: 1 AN: 60396

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.092	T
BayesDel_noAF	Benign	-0.37
CADD	Benign	16
DANN	Benign	0.65
DEOGEN2	Benign	0.038	T
Eigen	Benign	-0.65
Eigen_PC	Benign	-0.65
FATHMM_MKL	Benign	0.058	N
LIST_S2	Benign	0.58	T
M_CAP	Benign	0.0044	T
MetaRNN	Benign	0.086	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.0	M
PhyloP100		1.0
PROVEAN	Benign	-1.9	N
REVEL	Benign	0.091
Sift	Benign	0.39	T
Sift4G	Benign	0.48	T
Polyphen		0.23	B
Vest4		0.17
MutPred		0.50		Gain of sheet (P = 0.0221)
MVP		0.29
MPC		0.41
ClinPred		0.22	T
GERP RS		3.6
Varity_R		0.066
gMVP		0.50
Mutation Taster		=96/4	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs1028839934; hg19: chr2-219227485;