rs764508954

Variant names:

• chrX-55002382-C-G
• rs764508954
• NM_014481.4:c.373C>G

Your query was ambiguous. Multiple possible variants found:

• chrX-55002382-C-G
• chrX-55002382-C-T

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BS2

The NM_014481.4(APEX2):​c.373C>G​(p.Arg125Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000365 in 1,095,260 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 2 hemizygotes in GnomAD. 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. R125W) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 24)
  • Exomes 𝑓: 0.0000037 (0 hom. 2 hem.)
• Consequence: APEX2 NM_014481.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.86
• 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: Likely_benign. The variant received -4 ACMG points.

• BS2: High Hemizygotes in GnomAdExome4 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.373C>G	p.Arg125Gly	missense	Exon 3 of 6	NP_055296.2
	APEX2	NM_001271748.2		c.-91-580C>G		intron	N/A	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.373C>G	p.Arg125Gly	missense	Exon 3 of 6	ENSP00000364126.3	Q9UBZ4
	APEX2	ENST00000919358.1		c.373C>G	p.Arg125Gly	missense	Exon 3 of 6	ENSP00000589417.1
	APEX2	ENST00000886736.1		c.373C>G	p.Arg125Gly	missense	Exon 3 of 5	ENSP00000556795.1

Frequencies

GnomAD3 genomes Cov.: 24

GnomAD4 exome AF: 0.00000365 AC: 4 AN: 1095260 Hom.: 0 Cov.: 31 AF XY: 0.00000554 AC XY: 2 AN XY: 360862

African (AFR) AF: 0.00 AC: 0 AN: 26317

American (AMR) AF: 0.00 AC: 0 AN: 34767

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19164

East Asian (EAS) AF: 0.0000332 AC: 1 AN: 30156

South Asian (SAS) AF: 0.00 AC: 0 AN: 53413

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 40435

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4121

European-Non Finnish (NFE) AF: 0.00000357 AC: 3 AN: 840923

Other (OTH) AF: 0.00 AC: 0 AN: 45964

GnomAD4 genome Cov.: 24

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.077	T
BayesDel_noAF	Benign	-0.35
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.51	D
FATHMM_MKL	Uncertain	0.84	D
LIST_S2	Uncertain	0.90	D
M_CAP	Pathogenic	0.57	D
MetaRNN	Uncertain	0.66	D
MetaSVM	Benign	-0.53	T
MutationAssessor	Benign	1.4	L
PhyloP100		1.9
PrimateAI	Benign	0.47	T
PROVEAN	Uncertain	-3.4	D
REVEL	Benign	0.29
Sift	Uncertain	0.024	D
Sift4G	Benign	0.33	T
Polyphen		0.99	D
Vest4		0.28
MutPred		0.52		Gain of helix (P = 0.0225)
MVP		0.45
MPC		0.54
ClinPred		0.99	D
GERP RS		3.8
Varity_R		0.53
gMVP		0.55
Mutation Taster		=89/11	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		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: rs764508954; hg19: chrX-55028815;