rs3317

Variant names:

• chr5-112876454-G-A
• rs3317
• NM_005669.5:c.*2332C>T

Variant summary

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

The NM_005669.5(REEP5):​c.*2332C>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 0.434 in 152,024 control chromosomes in the GnomAD database, including 16,953 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 0.43 (16953 hom., cov: 32)
  • Failed GnomAD Quality Control
• Consequence: REEP5 NM_005669.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.239
• Publications: 23 publications found

Genes affected

REEP5 (HGNC:30077): (receptor accessory protein 5) Predicted to be involved in endoplasmic reticulum organization and regulation of intracellular transport. Located in endoplasmic reticulum tubular network. [provided by Alliance of Genome Resources, Apr 2022]

SRP19 (HGNC:11300): (signal recognition particle 19) Enables 7S RNA binding activity. Contributes to ribosome binding activity. Predicted to be involved in SRP-dependent cotranslational protein targeting to membrane, signal sequence recognition. Located in nucleolus. Part of signal recognition particle, endoplasmic reticulum targeting. [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=-0.82).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.64 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
REEP5	NM_005669.5	c.*2332C>T		3_prime_UTR_variant	Exon 5 of 5	ENST00000379638.9	NP_005660.4
SRP19	NM_001204199.2	c.301+11722G>A		intron_variant	Intron 4 of 4		NP_001191128.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
REEP5	ENST00000379638.9	c.*2332C>T		3_prime_UTR_variant	Exon 5 of 5	1	NM_005669.5	ENSP00000368959.4

Frequencies

GnomAD3 genomes AF: 0.434 AC: 65952 AN: 151906 Hom.: 16955 Cov.: 32

Gnomad AFR AF: 0.142

Gnomad AMI AF: 0.571

Gnomad AMR AF: 0.556

Gnomad ASJ AF: 0.501

Gnomad EAS AF: 0.659

Gnomad SAS AF: 0.571

Gnomad FIN AF: 0.517

Gnomad MID AF: 0.487

Gnomad NFE AF: 0.538

Gnomad OTH AF: 0.470

GnomAD4 exome Data not reliable, filtered out with message: AC0 AC: 0 AN: 0 Hom.: 0 Cov.: 0 AC XY: 0 AN XY: 0

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AC: 0 AN: 0

Other (OTH) AC: 0 AN: 0

GnomAD4 genome AF: 0.434 AC: 65949 AN: 152024 Hom.: 16953 Cov.: 32 AF XY: 0.438 AC XY: 32568 AN XY: 74314

African (AFR) AF: 0.142 AC: 5877 AN: 41484

American (AMR) AF: 0.556 AC: 8493 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.501 AC: 1735 AN: 3466

East Asian (EAS) AF: 0.658 AC: 3403 AN: 5168

South Asian (SAS) AF: 0.572 AC: 2755 AN: 4818

European-Finnish (FIN) AF: 0.517 AC: 5446 AN: 10536

Middle Eastern (MID) AF: 0.483 AC: 142 AN: 294

European-Non Finnish (NFE) AF: 0.538 AC: 36587 AN: 67962

Other (OTH) AF: 0.469 AC: 991 AN: 2114

Alfa AF: 0.509 Hom.: 63252

Bravo AF: 0.425

Asia WGS AF: 0.565 AC: 1961 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	3.8
DANN	Benign	0.58
PhyloP100		-0.24
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs3317; hg19: chr5-112212151;