chrX-135764277-C-G

Position:

• chrX-135764277-C-G

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_Strong BP6_Moderate

The NM_001370148.2(CT45A3):​c.168G>C​(p.Lys56Asn) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 7/10 in silico tools predict a benign outcome for this variant. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★).

• Frequency: Genomes: not found (cov: 0)
• Consequence: CT45A3 NM_001370148.2 missense, splice_region
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.08

Genes affected

CT45A3 (HGNC:33268): (cancer/testis antigen family 45 member A3) Predicted to be involved in snRNA 3'-end processing. Predicted to be part of integrator complex. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Likely_benign. Variant got -6 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.055775225).
• BP6: Variant X-135764277-C-G is Benign according to our data. Variant chrX-135764277-C-G is described in ClinVar as [Likely_benign]. Clinvar id is 2343109.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CT45A3	NM_001370148.2	c.168G>C	p.Lys56Asn	missense_variant, splice_region_variant	2/5	ENST00000598716.3	NP_001357077.1
CT45A3	NM_001017435.2	c.168G>C	p.Lys56Asn	missense_variant, splice_region_variant	2/5		NP_001017435.1
CT45A3	NM_001370149.1	c.168G>C	p.Lys56Asn	missense_variant, splice_region_variant	2/5		NP_001357078.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CT45A3	ENST00000598716.3	c.168G>C	p.Lys56Asn	missense_variant, splice_region_variant	2/5	3	NM_001370148.2	ENSP00000471571	P1
CT45A3	ENST00000597510.6	c.168G>C	p.Lys56Asn	missense_variant, splice_region_variant	1/4	1		ENSP00000471418	P1

Frequencies

GnomAD3 genomes Cov.: 0

GnomAD3 exomes AF: 0.00779 AC: 247 AN: 31710 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 7596

Gnomad AFR exome AF: 0.000538

Gnomad AMR exome AF: 0.0302

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00476

Gnomad SAS exome AF: 0.000568

Gnomad FIN exome AF: 0.00319

Gnomad NFE exome AF: 0.00172

Gnomad OTH exome AF: 0.0100

GnomAD4 exome Cov.: 0

GnomAD4 genome Cov.: 0

Alfa AF: 0.00506 Hom.: 0

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Oct 06, 2021

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.24
BayesDel_noAF	Benign	-1.0
CADD	Benign	1.3
DANN	Benign	0.36
DEOGEN2	Benign	0.026	T;T
LIST_S2	Benign	0.50	T;.
MetaRNN	Benign	0.056	T;T
Sift4G	Benign	0.35	T;T
Vest4		0.079
gMVP		0.024

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.090		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs1556580124; hg19: chrX-134887400;