rs148117957

Variant names:

• chr9-133417807-G-A
• rs148117957
• NM_020385.4:c.38C>T

Your query was ambiguous. Multiple possible variants found:

• chr9-133417807-G-A
• chr9-133417807-G-C

Variant summary

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

The NM_001279350.2(REXO4):​c.-196C>T variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000688 in 1,454,314 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: REXO4 NM_001279350.2 5_prime_UTR_premature_start_codon_gain
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.48

Genes affected

REXO4 (HGNC:12820): (REX4 homolog, 3'-5' exonuclease) Enables DNA binding activity and nuclease activity. Involved in DNA catabolic process, endonucleolytic; DNA catabolic process, exonucleolytic; and DNA repair. Located in nuclear speck and nucleolus. [provided by Alliance of Genome Resources, Apr 2022]

ADAMTS13 (HGNC:1366): (ADAM metallopeptidase with thrombospondin type 1 motif 13) This gene encodes a member of a family of proteins containing several distinct regions, including a metalloproteinase domain, a disintegrin-like domain, and a thrombospondin type 1 (TS) motif. The enzyme encoded by this gene specifically cleaves von Willebrand Factor (vWF). Defects in this gene are associated with thrombotic thrombocytopenic purpura. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jul 2013]

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=0.12087926).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
REXO4	NM_020385.4	c.38C>T	p.Pro13Leu	missense_variant	Exon 1 of 8	ENST00000371942.8	NP_065118.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
REXO4	ENST00000371942.8	c.38C>T	p.Pro13Leu	missense_variant	Exon 1 of 8	1	NM_020385.4	ENSP00000361010.3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.88e-7 AC: 1 AN: 1454314 Hom.: 0 Cov.: 32 AF XY: 0.00000138 AC XY: 1 AN XY: 723778

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: 8.99e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.091
BayesDel_addAF	Benign	-0.22	T
BayesDel_noAF	Benign	-0.55
CADD	Benign	15
DANN	Benign	0.92
DEOGEN2	Benign	0.0080	.;T;T
Eigen	Benign	-0.54
Eigen_PC	Benign	-0.69
FATHMM_MKL	Benign	0.13	N
LIST_S2	Benign	0.57	T;T;T
M_CAP	Benign	0.015	T
MetaRNN	Benign	0.12	T;T;T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	1.8	L;L;.
PrimateAI	Benign	0.35	T
PROVEAN	Benign	-1.7	N;N;N
REVEL	Benign	0.047
Sift	Uncertain	0.0010	D;D;D
Sift4G	Benign	0.11	T;T;.
Polyphen		0.84	P;P;.
Vest4		0.098
MutPred		0.16		Loss of glycosylation at P13 (P = 0.0244);Loss of glycosylation at P13 (P = 0.0244);Loss of glycosylation at P13 (P = 0.0244);
MVP		0.19
MPC		0.39
ClinPred		0.63	D
GERP RS		2.2
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.030
gMVP		0.088

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

LitVar

Other links and lift over

dbSNP: rs148117957; hg19: chr9-136282927;