rs3748348

Variant names:

• chr14-21033036-G-A
• rs3748348
• NM_001012264.4:c.*782C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001012264.4(RNASE13):​c.*782C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.364 in 450,934 control chromosomes in the GnomAD database, including 32,298 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 0.41 (13520 hom., cov: 31)
  • Exomes 𝑓: 0.34 (18778 hom.)
• Consequence: RNASE13 NM_001012264.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0350
• Publications: 14 publications found

Genes affected

RNASE13 (HGNC:25285): (ribonuclease A family member 13 (inactive)) Predicted to enable nucleic acid binding activity. Predicted to be located in extracellular region. [provided by Alliance of Genome Resources, Apr 2022]

ENSG00000255472 (HGNC:):

NDRG2 (HGNC:14460): (NDRG family member 2) This gene is a member of the N-myc downregulated gene family which belongs to the alpha/beta hydrolase superfamily. The protein encoded by this gene is a cytoplasmic protein that may play a role in neurite outgrowth. This gene may be involved in glioblastoma carcinogenesis. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Aug 2017]

TPPP2 (HGNC:19293): (tubulin polymerization promoting protein family member 2) Enables tubulin binding activity. Involved in regulation of flagellated sperm motility. Located in cytosol. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.551 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RNASE13	NM_001012264.4	c.*782C>T		3_prime_UTR_variant	Exon 2 of 2	ENST00000382951.4	NP_001012264.1
TPPP2	NM_173846.5	c.*959G>A		downstream_gene_variant		ENST00000321760.11	NP_776245.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RNASE13	ENST00000382951.4	c.*782C>T		3_prime_UTR_variant	Exon 2 of 2	1	NM_001012264.4	ENSP00000372410.3
TPPP2	ENST00000321760.11	c.*959G>A		downstream_gene_variant		1	NM_173846.5	ENSP00000317595.6

Frequencies

GnomAD3 genomes AF: 0.408 AC: 61988 AN: 151802 Hom.: 13501 Cov.: 31

Gnomad AFR AF: 0.557

Gnomad AMI AF: 0.228

Gnomad AMR AF: 0.306

Gnomad ASJ AF: 0.391

Gnomad EAS AF: 0.147

Gnomad SAS AF: 0.257

Gnomad FIN AF: 0.366

Gnomad MID AF: 0.385

Gnomad NFE AF: 0.382

Gnomad OTH AF: 0.398

GnomAD2 exomes AF: 0.317 AC: 39901 AN: 125740 AF XY: 0.317

Gnomad AFR exome AF: 0.565

Gnomad AMR exome AF: 0.207

Gnomad ASJ exome AF: 0.375

Gnomad EAS exome AF: 0.158

Gnomad FIN exome AF: 0.376

Gnomad NFE exome AF: 0.381

Gnomad OTH exome AF: 0.330

GnomAD4 exome AF: 0.342 AC: 102177 AN: 299012 Hom.: 18778 Cov.: 0 AF XY: 0.336 AC XY: 57308 AN XY: 170626

African (AFR) AF: 0.562 AC: 4544 AN: 8080

American (AMR) AF: 0.203 AC: 5332 AN: 26212

Ashkenazi Jewish (ASJ) AF: 0.374 AC: 3907 AN: 10454

East Asian (EAS) AF: 0.159 AC: 1454 AN: 9136

South Asian (SAS) AF: 0.269 AC: 15829 AN: 58924

European-Finnish (FIN) AF: 0.372 AC: 4552 AN: 12236

Middle Eastern (MID) AF: 0.441 AC: 1177 AN: 2670

European-Non Finnish (NFE) AF: 0.384 AC: 60371 AN: 157364

Other (OTH) AF: 0.360 AC: 5011 AN: 13936

GnomAD4 genome AF: 0.408 AC: 62054 AN: 151922 Hom.: 13520 Cov.: 31 AF XY: 0.401 AC XY: 29810 AN XY: 74278

African (AFR) AF: 0.557 AC: 23021 AN: 41356

American (AMR) AF: 0.305 AC: 4666 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.391 AC: 1356 AN: 3468

East Asian (EAS) AF: 0.146 AC: 756 AN: 5170

South Asian (SAS) AF: 0.258 AC: 1243 AN: 4816

European-Finnish (FIN) AF: 0.366 AC: 3867 AN: 10552

Middle Eastern (MID) AF: 0.401 AC: 118 AN: 294

European-Non Finnish (NFE) AF: 0.382 AC: 25975 AN: 67952

Other (OTH) AF: 0.400 AC: 844 AN: 2110

Alfa AF: 0.386 Hom.: 23974

Bravo AF: 0.410

Asia WGS AF: 0.221 AC: 768 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	6.4
DANN	Benign	0.72
PhyloP100		0.035
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs3748348; hg19: chr14-21501195;