chrX-55001565-C-T

Variant names:

• chrX-55001565-C-T
• rs61752442
• NM_014481.4:c.177C>T

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 0P and 11B. BP4_Strong BP6_Moderate BP7 BS2

The NM_014481.4(APEX2):​c.177C>T​(p.Pro59Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00806 in 1,204,475 control chromosomes in the GnomAD database, including 33 homozygotes. There are 3,058 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0063 (2 hom., 217 hem., cov: 23)
  • Exomes 𝑓: 0.0082 (31 hom. 2841 hem.)
• Consequence: APEX2 NM_014481.4 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.552
• Publications: 3 publications found

Genes affected

APEX2 (HGNC:17889): (apurinic/apyrimidinic endodeoxyribonuclease 2) Apurinic/apyrimidinic (AP) sites occur frequently in DNA molecules by spontaneous hydrolysis, by DNA damaging agents or by DNA glycosylases that remove specific abnormal bases. AP sites are pre-mutagenic lesions that can prevent normal DNA replication so the cell contains systems to identify and repair such sites. Class II AP endonucleases cleave the phosphodiester backbone 5' to the AP site. This gene encodes a protein shown to have a weak class II AP endonuclease activity. Most of the encoded protein is located in the nucleus but some is also present in mitochondria. This protein may play an important role in both nuclear and mitochondrial base excision repair. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene. [provided by RefSeq, Nov 2012]

ACMG classification

Our verdict: Benign. The variant received -11 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.73).
• BP6: Variant X-55001565-C-T is Benign according to our data. Variant chrX-55001565-C-T is described in ClinVar as Benign. ClinVar VariationId is 718857.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-0.552 with no splicing effect.
• BS2: High Homozygotes in GnomAd4 at 2 gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014481.4. 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
	APEX2	NM_014481.4	MANE Select	c.177C>T	p.Pro59Pro	synonymous	Exon 2 of 6	NP_055296.2
	APEX2	NM_001271748.2		c.-156C>T		5_prime_UTR	Exon 2 of 5	NP_001258677.1	B7ZA71

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	APEX2	ENST00000374987.4	TSL:1 MANE Select	c.177C>T	p.Pro59Pro	synonymous	Exon 2 of 6	ENSP00000364126.3	Q9UBZ4
	APEX2	ENST00000919358.1		c.177C>T	p.Pro59Pro	synonymous	Exon 2 of 6	ENSP00000589417.1
	APEX2	ENST00000886736.1		c.177C>T	p.Pro59Pro	synonymous	Exon 2 of 5	ENSP00000556795.1

Frequencies

GnomAD3 genomes AF: 0.00626 AC: 696 AN: 111123 Hom.: 2 Cov.: 23

Gnomad AFR AF: 0.000919

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000860

Gnomad ASJ AF: 0.00189

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.0208

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00992

Gnomad OTH AF: 0.00331

GnomAD2 exomes AF: 0.00640 AC: 1089 AN: 170201 AF XY: 0.00541

Gnomad AFR exome AF: 0.00186

Gnomad AMR exome AF: 0.00131

Gnomad ASJ exome AF: 0.00125

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.0207

Gnomad NFE exome AF: 0.00914

Gnomad OTH exome AF: 0.00471

GnomAD4 exome AF: 0.00824 AC: 9014 AN: 1093300 Hom.: 31 Cov.: 29 AF XY: 0.00791 AC XY: 2841 AN XY: 359180

African (AFR) AF: 0.00141 AC: 37 AN: 26316

American (AMR) AF: 0.00153 AC: 53 AN: 34711

Ashkenazi Jewish (ASJ) AF: 0.00182 AC: 35 AN: 19272

East Asian (EAS) AF: 0.00 AC: 0 AN: 30057

South Asian (SAS) AF: 0.0000754 AC: 4 AN: 53050

European-Finnish (FIN) AF: 0.0187 AC: 753 AN: 40205

Middle Eastern (MID) AF: 0.000971 AC: 4 AN: 4120

European-Non Finnish (NFE) AF: 0.00937 AC: 7865 AN: 839655

Other (OTH) AF: 0.00573 AC: 263 AN: 45914

GnomAD4 genome AF: 0.00626 AC: 696 AN: 111175 Hom.: 2 Cov.: 23 AF XY: 0.00650 AC XY: 217 AN XY: 33363

African (AFR) AF: 0.000917 AC: 28 AN: 30542

American (AMR) AF: 0.000859 AC: 9 AN: 10480

Ashkenazi Jewish (ASJ) AF: 0.00189 AC: 5 AN: 2648

East Asian (EAS) AF: 0.00 AC: 0 AN: 3523

South Asian (SAS) AF: 0.00 AC: 0 AN: 2622

European-Finnish (FIN) AF: 0.0208 AC: 123 AN: 5920

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 218

European-Non Finnish (NFE) AF: 0.00992 AC: 526 AN: 53011

Other (OTH) AF: 0.00327 AC: 5 AN: 1529

Alfa AF: 0.00863 Hom.: 55

Bravo AF: 0.00435

ClinVar

ClinVar submissions

Significance: 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
BayesDel_noAF	Benign	-0.73
CADD	Benign	5.4
DANN	Benign	0.77
PhyloP100		-0.55
Mutation Taster		=100/0	polymorphism (auto)

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: rs61752442; hg19: chrX-55027998; COSMIC: COSV100895230; COSMIC: COSV100895230;