2-218367080-T-C

Position:

• chr2-218367080-T-C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The ENST00000289388.4(CATIP):​c.812T>C​(p.Met271Thr) 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 benign outcome for this variant. 12/19 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)
• Consequence: CATIP ENST00000289388.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.41

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]

CATIP-AS1 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.09156543).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CATIP	NM_198559.2	c.812T>C	p.Met271Thr	missense_variant	8/10	ENST00000289388.4	NP_940961.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CATIP	ENST00000289388.4	c.812T>C	p.Met271Thr	missense_variant	8/10	1	NM_198559.2	ENSP00000289388.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 29

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Aug 11, 2022

The c.812T>C (p.M271T) alteration is located in exon 8 (coding exon 8) of the CATIP gene. This alteration results from a T to C substitution at nucleotide position 812, causing the methionine (M) at amino acid position 271 to be replaced by a threonine (T). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.51
BayesDel_addAF	Benign	-0.057	T
BayesDel_noAF	Benign	-0.32
CADD	Benign	22
DANN	Benign	0.95
DEOGEN2	Benign	0.084	T
Eigen	Benign	-0.13
Eigen_PC	Benign	0.010
FATHMM_MKL	Benign	0.69	D
LIST_S2	Benign	0.60	T
M_CAP	Benign	0.0034	T
MetaRNN	Benign	0.092	T
MetaSVM	Benign	-0.84	T
MutationAssessor	Uncertain	2.0	M
MutationTaster	Benign	0.84	D
PROVEAN	Benign	-2.2	N
REVEL	Benign	0.043
Sift	Benign	0.26	T
Sift4G	Benign	0.20	T
Polyphen		0.020	B
Vest4		0.21
MutPred		0.40		Gain of methylation at K270 (P = 0.0283);
MVP		0.45
MPC		0.73
ClinPred		0.78	D
GERP RS		4.7
Varity_R		0.32
gMVP		0.40

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr2-219231803;