rs200032355

Variant names:

• chr2-68502857-C-A
• NM_173545.3:c.295C>A

Your query was ambiguous. Multiple possible variants found:

• chr2-68502857-C-A
• chr2-68502857-C-G
• chr2-68502857-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_173545.3(APLF):​c.295C>A​(p.Arg99Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000688 in 1,454,124 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. 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. R99C) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: APLF NM_173545.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.501

Genes affected

APLF (HGNC:28724): (aprataxin and PNKP like factor) Enables DNA-(apurinic or apyrimidinic site) endonuclease activity; nuclease activity; and nucleotide binding activity. Involved in double-strand break repair via nonhomologous end joining and single strand break repair. Acts upstream of or within positive regulation of DNA ligation. Located in nucleoplasm. Is active in site of double-strand break. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.18809658).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
APLF	NM_173545.3	c.295C>A	p.Arg99Ser	missense_variant	Exon 3 of 10	ENST00000303795.9	NP_775816.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
APLF	ENST00000303795.9	c.295C>A	p.Arg99Ser	missense_variant	Exon 3 of 10	1	NM_173545.3	ENSP00000307004.4
APLF	ENST00000445692.5	n.295C>A		non_coding_transcript_exon_variant	Exon 3 of 11	5		ENSP00000393403.1
APLF	ENST00000529851.5	n.223C>A		non_coding_transcript_exon_variant	Exon 2 of 9	5		ENSP00000432297.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.88e-7 AC: 1 AN: 1454124 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 723518

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.0000167

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.22
BayesDel_addAF	Benign	-0.13	T
BayesDel_noAF	Benign	-0.43
CADD	Benign	3.5
DANN	Uncertain	0.98
DEOGEN2	Benign	0.17	T
Eigen	Benign	-0.27
Eigen_PC	Benign	-0.44
FATHMM_MKL	Benign	0.058	N
LIST_S2	Benign	0.63	T
M_CAP	Benign	0.0066	T
MetaRNN	Benign	0.19	T
MetaSVM	Benign	-0.98	T
MutationAssessor	Uncertain	2.3	M
PrimateAI	Benign	0.21	T
PROVEAN	Uncertain	-2.6	D
REVEL	Benign	0.13
Sift	Benign	0.077	T
Sift4G	Uncertain	0.027	D
Polyphen		0.83	P
Vest4		0.22
MutPred		0.46		Gain of methylation at K95 (P = 0.0477);
MVP		0.17
MPC		0.043
ClinPred		0.65	D
GERP RS		1.4
Varity_R		0.61
gMVP		0.56

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr2-68729989;