chrX-55006805-A-G

Variant names:

• chrX-55006805-A-G
• rs6651872
• NM_014481.4:c.927A>G

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_014481.4(APEX2):​c.927A>G​(p.Ala309Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00273 in 1,210,044 control chromosomes in the GnomAD database, including 57 homozygotes. There are 893 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.015 (39 hom., 457 hem., cov: 22)
  • Exomes 𝑓: 0.0015 (18 hom. 436 hem.)
• Consequence: APEX2 NM_014481.4 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.213
• Publications: 0 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 -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BP6: Variant X-55006805-A-G is Benign according to our data. Variant chrX-55006805-A-G is described in ClinVar as Benign. ClinVar VariationId is 782675.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=0.213 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0504 is higher than 0.05.

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.927A>G	p.Ala309Ala	synonymous	Exon 6 of 6	NP_055296.2
	APEX2	NM_001271748.2		c.414A>G	p.Ala138Ala	synonymous	Exon 5 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.927A>G	p.Ala309Ala	synonymous	Exon 6 of 6	ENSP00000364126.3	Q9UBZ4
	APEX2	ENST00000919358.1		c.882A>G	p.Ala294Ala	synonymous	Exon 6 of 6	ENSP00000589417.1
	APEX2	ENST00000886736.1		c.780A>G	p.Ala260Ala	synonymous	Exon 5 of 5	ENSP00000556795.1

Frequencies

GnomAD3 genomes AF: 0.0150 AC: 1675 AN: 111930 Hom.: 39 Cov.: 22

Gnomad AFR AF: 0.0525

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00433

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000370

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000564

Gnomad OTH AF: 0.00863

GnomAD2 exomes AF: 0.00420 AC: 766 AN: 182337 AF XY: 0.00272

Gnomad AFR exome AF: 0.0532

Gnomad AMR exome AF: 0.00179

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000861

Gnomad OTH exome AF: 0.00266

GnomAD4 exome AF: 0.00148 AC: 1622 AN: 1098062 Hom.: 18 Cov.: 31 AF XY: 0.00120 AC XY: 436 AN XY: 363420

African (AFR) AF: 0.0512 AC: 1353 AN: 26403

American (AMR) AF: 0.00242 AC: 85 AN: 35186

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19379

East Asian (EAS) AF: 0.00 AC: 0 AN: 30203

South Asian (SAS) AF: 0.0000740 AC: 4 AN: 54079

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 40525

Middle Eastern (MID) AF: 0.00266 AC: 11 AN: 4137

European-Non Finnish (NFE) AF: 0.0000131 AC: 11 AN: 842064

Other (OTH) AF: 0.00343 AC: 158 AN: 46086

GnomAD4 genome AF: 0.0150 AC: 1678 AN: 111982 Hom.: 39 Cov.: 22 AF XY: 0.0134 AC XY: 457 AN XY: 34174

African (AFR) AF: 0.0525 AC: 1615 AN: 30772

American (AMR) AF: 0.00433 AC: 46 AN: 10634

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2643

East Asian (EAS) AF: 0.00 AC: 0 AN: 3547

South Asian (SAS) AF: 0.000371 AC: 1 AN: 2693

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 6127

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 219

European-Non Finnish (NFE) AF: 0.0000565 AC: 3 AN: 53138

Other (OTH) AF: 0.00852 AC: 13 AN: 1526

Alfa AF: 0.00834 Hom.: 69

Bravo AF: 0.0172

EpiCase AF: 0.0000545

EpiControl AF: 0.000119

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	6.4
DANN	Benign	0.75
PhyloP100		0.21
Mutation Taster		=100/0	polymorphism (auto)

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: rs6651872; hg19: chrX-55033238;