2-218367732-G-A

Variant names:

• chr2-218367732-G-A
• NM_198559.2:c.932G>A

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.932G>A​(p.Arg311Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000691 in 1,446,544 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/20 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: 6.9e-7 (0 hom.)
• Consequence: CATIP NM_198559.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.40
• 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]

CATIP-AS1 (HGNC:41080): (CATIP antisense RNA 1)

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=0.18737397).

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.932G>A	p.Arg311Gln	missense	Exon 10 of 10	NP_940961.1	Q7Z7H3
	CATIP	NM_001320865.2		c.965G>A	p.Arg322Gln	missense	Exon 10 of 10	NP_001307794.1
	CATIP-AS1	NR_110573.1		n.171C>T		non_coding_transcript_exon	Exon 1 of 3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CATIP	ENST00000289388.4	TSL:1 MANE Select	c.932G>A	p.Arg311Gln	missense	Exon 10 of 10	ENSP00000289388.3	Q7Z7H3
	CATIP-AS1	ENST00000441749.3	TSL:1	n.175C>T		non_coding_transcript_exon	Exon 1 of 3
	CATIP	ENST00000851696.1		c.965G>A	p.Arg322Gln	missense	Exon 10 of 10	ENSP00000521755.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.91e-7 AC: 1 AN: 1446544 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 719324

African (AFR) AF: 0.00 AC: 0 AN: 33186

American (AMR) AF: 0.00 AC: 0 AN: 43006

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25824

East Asian (EAS) AF: 0.00 AC: 0 AN: 38996

South Asian (SAS) AF: 0.0000118 AC: 1 AN: 84866

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 47236

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5700

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1107846

Other (OTH) AF: 0.00 AC: 0 AN: 59884

GnomAD4 genome Cov.: 32

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	0.11
BayesDel_addAF	Benign	-0.075	T
BayesDel_noAF	Benign	-0.34
CADD	Uncertain	25
DANN	Benign	0.94
DEOGEN2	Benign	0.047	T
Eigen	Benign	-0.35
Eigen_PC	Benign	-0.41
FATHMM_MKL	Benign	0.53	D
LIST_S2	Benign	0.80	T
M_CAP	Benign	0.051	D
MetaRNN	Benign	0.19	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.4	M
PhyloP100		2.4
PROVEAN	Benign	-0.77	N
REVEL	Benign	0.046
Sift	Benign	0.30	T
Sift4G	Benign	0.34	T
Polyphen		0.89	P
Vest4		0.13
MutPred		0.30		Gain of ubiquitination at K307 (P = 0.1067)
MVP		0.55
MPC		0.80
ClinPred		0.71	D
GERP RS		2.8
Varity_R		0.10
gMVP		0.58
Mutation Taster		=98/2	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.16		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

hg19: chr2-219232455;