chr2-218357691-C-G

Variant names:

• chr2-218357691-C-G
• rs1200960981
• NM_198559.2:c.276C>G

Variant summary

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

The NM_198559.2(CATIP):​c.276C>G​(p.Ser92Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,798 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: CATIP NM_198559.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.54
• 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-AS2 (HGNC:41079): (CATIP antisense RNA 2)

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, 0.897

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.276C>G	p.Ser92Arg	missense	Exon 3 of 10	NP_940961.1	Q7Z7H3
	CATIP	NM_001320865.2		c.309C>G	p.Ser103Arg	missense	Exon 3 of 10	NP_001307794.1
	CATIP-AS2	NR_125777.1		n.53+223G>C		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CATIP	ENST00000289388.4	TSL:1 MANE Select	c.276C>G	p.Ser92Arg	missense	Exon 3 of 10	ENSP00000289388.3	Q7Z7H3
	CATIP	ENST00000851696.1		c.309C>G	p.Ser103Arg	missense	Exon 3 of 10	ENSP00000521755.1
	CATIP	ENST00000851694.1		c.183C>G	p.Ser61Arg	missense	Exon 2 of 9	ENSP00000521753.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461798 Hom.: 0 Cov.: 32 AF XY: 0.00000138 AC XY: 1 AN XY: 727198

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

American (AMR) AF: 0.00 AC: 0 AN: 44722

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53356

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5746

European-Non Finnish (NFE) AF: 8.99e-7 AC: 1 AN: 1112008

Other (OTH) AF: 0.00 AC: 0 AN: 60392

GnomAD4 genome Cov.: 31

Alfa AF: 0.0000283 Hom.: 0

Bravo AF: 0.00000378

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	Pathogenic	0.80
BayesDel_addAF	Uncertain	0.10	D
BayesDel_noAF	Benign	-0.090
CADD	Benign	22
DANN	Uncertain	0.99
DEOGEN2	Uncertain	0.45	T
Eigen	Benign	-0.31
Eigen_PC	Benign	-0.43
FATHMM_MKL	Benign	0.38	N
LIST_S2	Benign	0.68	T
M_CAP	Benign	0.031	D
MetaRNN	Pathogenic	0.90	D
MetaSVM	Benign	-0.94	T
MutationAssessor	Pathogenic	2.9	M
PhyloP100		2.5
PROVEAN	Uncertain	-3.7	D
REVEL	Uncertain	0.47
Sift	Uncertain	0.016	D
Sift4G	Uncertain	0.0030	D
Polyphen		0.67	P
Vest4		0.62
MutPred		0.74		Loss of sheet (P = 0.0357)
MVP		0.42
MPC		0.77
ClinPred		0.98	D
GERP RS		3.0
Varity_R		0.54
gMVP		0.93
Mutation Taster		=98/2	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.10		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: rs1200960981; hg19: chr2-219222414;