rs142470785

Variant names:

• chr2-218367887-G-A
• rs142470785
• NM_198559.2:c.1087G>A

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_Strong BS2

The NM_198559.2(CATIP):​c.1087G>A​(p.Ala363Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000888 in 1,612,622 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★).

• Frequency:
  • Genomes: 𝑓 0.00056 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00092 (3 hom.)
• Consequence: CATIP NM_198559.2 missense
• Clinical Significance: Uncertain significance criteria provided, multiple submitters, no conflicts U:2
• Conservation: PhyloP100: -1.07
• Publications: 1 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: Benign. The variant received -8 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.008692443).
• BS2: High Homozygotes in GnomAdExome4 at 3 AR gene

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.1087G>A	p.Ala363Thr	missense	Exon 10 of 10	NP_940961.1	Q7Z7H3
	CATIP	NM_001320865.2		c.1120G>A	p.Ala374Thr	missense	Exon 10 of 10	NP_001307794.1
	CATIP-AS1	NR_110573.1		n.16C>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.1087G>A	p.Ala363Thr	missense	Exon 10 of 10	ENSP00000289388.3	Q7Z7H3
	CATIP-AS1	ENST00000441749.3	TSL:1	n.20C>T		non_coding_transcript_exon	Exon 1 of 3
	CATIP	ENST00000851696.1		c.1120G>A	p.Ala374Thr	missense	Exon 10 of 10	ENSP00000521755.1

Frequencies

GnomAD3 genomes AF: 0.000565 AC: 86 AN: 152248 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000241

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000196

Gnomad ASJ AF: 0.000288

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000188

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00103

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000438 AC: 108 AN: 246340 AF XY: 0.000417

Gnomad AFR exome AF: 0.000256

Gnomad AMR exome AF: 0.000261

Gnomad ASJ exome AF: 0.000100

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.0000474

Gnomad NFE exome AF: 0.000805

Gnomad OTH exome AF: 0.000661

GnomAD4 exome AF: 0.000922 AC: 1346 AN: 1460256 Hom.: 3 Cov.: 32 AF XY: 0.000849 AC XY: 617 AN XY: 726522

African (AFR) AF: 0.000209 AC: 7 AN: 33458

American (AMR) AF: 0.000268 AC: 12 AN: 44700

Ashkenazi Jewish (ASJ) AF: 0.0000383 AC: 1 AN: 26102

East Asian (EAS) AF: 0.00 AC: 0 AN: 39686

South Asian (SAS) AF: 0.0000232 AC: 2 AN: 86216

European-Finnish (FIN) AF: 0.0000383 AC: 2 AN: 52212

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5726

European-Non Finnish (NFE) AF: 0.00112 AC: 1243 AN: 1111798

Other (OTH) AF: 0.00131 AC: 79 AN: 60358

GnomAD4 genome AF: 0.000564 AC: 86 AN: 152366 Hom.: 0 Cov.: 32 AF XY: 0.000591 AC XY: 44 AN XY: 74506

African (AFR) AF: 0.000240 AC: 10 AN: 41586

American (AMR) AF: 0.000196 AC: 3 AN: 15312

Ashkenazi Jewish (ASJ) AF: 0.000288 AC: 1 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5182

South Asian (SAS) AF: 0.00 AC: 0 AN: 4832

European-Finnish (FIN) AF: 0.000188 AC: 2 AN: 10626

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00103 AC: 70 AN: 68038

Other (OTH) AF: 0.00 AC: 0 AN: 2114

Alfa AF: 0.000851 Hom.: 0

Bravo AF: 0.000586

TwinsUK AF: 0.00189 AC: 7

ALSPAC AF: 0.00104 AC: 4

ESP6500AA AF: 0.000227 AC: 1

ESP6500EA AF: 0.00105 AC: 9

ExAC AF: 0.000421 AC: 51

EpiCase AF: 0.000600

EpiControl AF: 0.00148

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	1	-	not provided (1)
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.091
BayesDel_addAF	Benign	-0.61	T
BayesDel_noAF	Benign	-0.66
CADD	Benign	2.1
DANN	Benign	0.97
DEOGEN2	Benign	0.025	T
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.30	N
LIST_S2	Benign	0.48	T
M_CAP	Benign	0.031	D
MetaRNN	Benign	0.0087	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.9	M
PhyloP100		-1.1
PROVEAN	Benign	-0.99	N
REVEL	Benign	0.022
Sift	Benign	0.098	T
Sift4G	Benign	0.44	T
Polyphen		0.069	B
Vest4		0.090
MVP		0.16
MPC		0.34
ClinPred		0.030	T
GERP RS		-6.9
Varity_R		0.053
gMVP		0.34
Mutation Taster		=98/2	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: rs142470785; hg19: chr2-219232610; COSMIC: COSV56823290; COSMIC: COSV56823290;