NM_198559.2:c.751G>C

Variant names:

• chr2-218364748-G-C
• rs566817286
• NM_198559.2:c.751G>C

Variant summary

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

The NM_198559.2(CATIP):​c.751G>C​(p.Asp251His) variant causes a missense change. The variant allele was found at a frequency of 0.00000656 in 152,326 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. D251N) has been classified as Uncertain significance.

• Frequency: Genomes: 𝑓 0.0000066 (0 hom., cov: 33)
• Consequence: CATIP NM_198559.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.59
• 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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

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.751G>C	p.Asp251His	missense	Exon 7 of 10	NP_940961.1	Q7Z7H3
	CATIP	NM_001320865.2		c.784G>C	p.Asp262His	missense	Exon 7 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.751G>C	p.Asp251His	missense	Exon 7 of 10	ENSP00000289388.3	Q7Z7H3
	CATIP	ENST00000851696.1		c.784G>C	p.Asp262His	missense	Exon 7 of 10	ENSP00000521755.1
	CATIP	ENST00000851694.1		c.658G>C	p.Asp220His	missense	Exon 6 of 9	ENSP00000521753.1

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152208 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.00000401 AC: 1 AN: 249506 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: 0.0000548

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome Cov.: 31

GnomAD4 genome AF: 0.00000656 AC: 1 AN: 152326 Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0 AN XY: 74472

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 41582

American (AMR) AF: 0.00 AC: 0 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5178

South Asian (SAS) AF: 0.00 AC: 0 AN: 4826

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10616

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

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68030

Other (OTH) AF: 0.00 AC: 0 AN: 2116

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

ExAC AF: 0.00000824 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.86
BayesDel_addAF	Uncertain	0.13	D
BayesDel_noAF	Uncertain	0.12
CADD	Pathogenic	26
DANN	Uncertain	0.99
DEOGEN2	Benign	0.31	T
Eigen	Uncertain	0.57
Eigen_PC	Uncertain	0.50
FATHMM_MKL	Uncertain	0.91	D
LIST_S2	Benign	0.78	T
M_CAP	Benign	0.010	T
MetaRNN	Uncertain	0.65	D
MetaSVM	Uncertain	-0.16	T
MutationAssessor	Uncertain	2.6	M
PhyloP100		3.6
PROVEAN	Pathogenic	-4.7	D
REVEL	Uncertain	0.37
Sift	Uncertain	0.0040	D
Sift4G	Pathogenic	0.0	D
Polyphen		0.99	D
Vest4		0.67
MutPred		0.63		Loss of sheet (P = 0.0054)
MVP		0.62
MPC		0.95
ClinPred		0.99	D
GERP RS		4.5
Varity_R		0.65
gMVP		0.75
Mutation Taster		=72/28	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: rs566817286; hg19: chr2-219229471;