chr2-218367747-G-C

Variant names:

• chr2-218367747-G-C
• rs139704670
• NM_198559.2:c.947G>C

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

The NM_198559.2(CATIP):​c.947G>C​(p.Ser316Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000462 in 1,606,638 control chromosomes in the GnomAD database, including 6 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0024 (4 hom., cov: 32)
  • Exomes 𝑓: 0.00025 (2 hom.)
• Consequence: CATIP NM_198559.2 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 2.15
• 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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.00785625).
• BP6: Variant 2-218367747-G-C is Benign according to our data. Variant chr2-218367747-G-C is described in ClinVar as Likely_benign. ClinVar VariationId is 2651876.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Homozygotes in GnomAd4 at 4 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.947G>C	p.Ser316Thr	missense	Exon 10 of 10	NP_940961.1	Q7Z7H3
	CATIP	NM_001320865.2		c.980G>C	p.Ser327Thr	missense	Exon 10 of 10	NP_001307794.1
	CATIP-AS1	NR_110573.1		n.156C>G		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.947G>C	p.Ser316Thr	missense	Exon 10 of 10	ENSP00000289388.3	Q7Z7H3
	CATIP-AS1	ENST00000441749.3	TSL:1	n.160C>G		non_coding_transcript_exon	Exon 1 of 3
	CATIP	ENST00000851696.1		c.980G>C	p.Ser327Thr	missense	Exon 10 of 10	ENSP00000521755.1

Frequencies

GnomAD3 genomes AF: 0.00240 AC: 365 AN: 152186 Hom.: 4 Cov.: 32

Gnomad AFR AF: 0.00779

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00222

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.0000588

Gnomad OTH AF: 0.000955

GnomAD2 exomes AF: 0.000553 AC: 130 AN: 235128 AF XY: 0.000465

Gnomad AFR exome AF: 0.00738

Gnomad AMR exome AF: 0.000474

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000189

Gnomad OTH exome AF: 0.000345

GnomAD4 exome AF: 0.000254 AC: 370 AN: 1454334 Hom.: 2 Cov.: 32 AF XY: 0.000224 AC XY: 162 AN XY: 723592

African (AFR) AF: 0.00737 AC: 246 AN: 33356

American (AMR) AF: 0.000520 AC: 23 AN: 44258

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26000

East Asian (EAS) AF: 0.00 AC: 0 AN: 39478

South Asian (SAS) AF: 0.0000817 AC: 7 AN: 85706

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 48952

Middle Eastern (MID) AF: 0.00104 AC: 6 AN: 5754

European-Non Finnish (NFE) AF: 0.0000360 AC: 40 AN: 1110686

Other (OTH) AF: 0.000798 AC: 48 AN: 60144

GnomAD4 genome AF: 0.00244 AC: 372 AN: 152304 Hom.: 4 Cov.: 32 AF XY: 0.00255 AC XY: 190 AN XY: 74464

African (AFR) AF: 0.00794 AC: 330 AN: 41576

American (AMR) AF: 0.00222 AC: 34 AN: 15310

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 5162

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4828

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10620

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.0000588 AC: 4 AN: 68016

Other (OTH) AF: 0.000945 AC: 2 AN: 2116

Alfa AF: 0.000399 Hom.: 0

Bravo AF: 0.00251

ESP6500AA AF: 0.00344 AC: 15

ESP6500EA AF: 0.00 AC: 0

ExAC AF: 0.000702 AC: 85

Asia WGS AF: 0.00202 AC: 7 AN: 3478

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.086
BayesDel_addAF	Benign	-0.51	T
BayesDel_noAF	Benign	-0.49
CADD	Benign	17
DANN	Benign	0.51
DEOGEN2	Benign	0.027	T
Eigen	Benign	-0.85
Eigen_PC	Benign	-0.85
FATHMM_MKL	Benign	0.25	N
LIST_S2	Benign	0.49	T
MetaRNN	Benign	0.0079	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.3	L
PhyloP100		2.2
PROVEAN	Benign	-0.070	N
REVEL	Benign	0.12
Sift	Benign	0.73	T
Sift4G	Benign	0.96	T
Polyphen		0.047	B
Vest4		0.10
MVP		0.31
MPC		0.35
ClinPred		0.031	T
GERP RS		1.9
Varity_R		0.16
gMVP		0.39
Mutation Taster		=99/1	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: rs139704670; hg19: chr2-219232470;