rs7639267

chr3-52534789-G-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000492555.5(NT5DC2):c.-136C>A variant causes a 5 prime UTR, NMD transcript change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.552 in 1,111,396 control chromosomes in the GnomAD database, including 172,965 homozygotes. 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: 𝑓 0.59 (26515 hom., cov: 33)
  • Exomes 𝑓: 0.55 (146450 hom.)
• Consequence: NT5DC2 ENST00000492555.5 5_prime_UTR, NMD_transcript
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0160

Genes affected

NT5DC2 (HGNC:25717): (5'-nucleotidase domain containing 2) Predicted to enable 5'-nucleotidase activity. Predicted to be involved in dephosphorylation. [provided by Alliance of Genome Resources, Apr 2022]

UQCC5 (HGNC:37257): (ubiquinol-cytochrome c reductase complex assembly factor 5) Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.651 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NT5DC2	NM_022908.3	c.-136C>A		5_prime_UTR_variant	1/14
NT5DC2	XM_047448760.1	c.-136C>A		5_prime_UTR_variant	1/14

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NT5DC2	ENST00000492555.5	c.-136C>A		5_prime_UTR_variant, NMD_transcript_variant	1/13	1
NT5DC2	ENST00000307076.8	c.-136C>A		5_prime_UTR_variant	1/14	2		A2
UQCC5	ENST00000482728.1	n.265G>T		non_coding_transcript_exon_variant	1/2	2
UQCC5	ENST00000491607.5	n.137-14G>T		splice_polypyrimidine_tract_variant, intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.586 AC: 88968 AN: 151944 Hom.: 26477 Cov.: 33

Gnomad AFR AF: 0.657

Gnomad AMI AF: 0.575

Gnomad AMR AF: 0.643

Gnomad ASJ AF: 0.552

Gnomad EAS AF: 0.452

Gnomad SAS AF: 0.333

Gnomad FIN AF: 0.545

Gnomad MID AF: 0.592

Gnomad NFE AF: 0.565

Gnomad OTH AF: 0.579

GnomAD4 exome AF: 0.547 AC: 524569 AN: 959334 Hom.: 146450 Cov.: 13 AF XY: 0.539 AC XY: 261009 AN XY: 484374

Gnomad4 AFR exome AF: 0.668

Gnomad4 AMR exome AF: 0.650

Gnomad4 ASJ exome AF: 0.551

Gnomad4 EAS exome AF: 0.493

Gnomad4 SAS exome AF: 0.339

Gnomad4 FIN exome AF: 0.554

Gnomad4 NFE exome AF: 0.560

Gnomad4 OTH exome AF: 0.540

GnomAD4 genome AF: 0.586 AC: 89065 AN: 152062 Hom.: 26515 Cov.: 33 AF XY: 0.581 AC XY: 43187 AN XY: 74324

Gnomad4 AFR AF: 0.658

Gnomad4 AMR AF: 0.643

Gnomad4 ASJ AF: 0.552

Gnomad4 EAS AF: 0.452

Gnomad4 SAS AF: 0.333

Gnomad4 FIN AF: 0.545

Gnomad4 NFE AF: 0.565

Gnomad4 OTH AF: 0.583

Alfa AF: 0.580 Hom.: 8023

Bravo AF: 0.600

Asia WGS AF: 0.456 AC: 1590 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
Cadd	Benign	4.6
Dann	Benign	0.63

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: rs7639267; hg19: chr3-52568805;