5-112887090-C-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_005669.5(REEP5):c.445G>A(p.Glu149Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0125 in 1,613,564 control chromosomes in the GnomAD database, including 175 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.011 (8 hom., cov: 32)
  • Exomes 𝑓: 0.013 (167 hom.)
• Consequence: REEP5 NM_005669.5 missense
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 2.25

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

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0070326924).
• BP6: Variant 5-112887090-C-T is Benign according to our data. Variant chr5-112887090-C-T is described in ClinVar as [Benign]. Clinvar id is 2655638.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population amr. gnomad4 allele frequency = 0.0112 (1711/152260) while in subpopulation AMR AF= 0.0167 (256/15286). AF 95% confidence interval is 0.0151. There are 8 homozygotes in gnomad4. There are 817 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 8 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
REEP5	NM_005669.5	c.445G>A	p.Glu149Lys	missense_variant	4/5	ENST00000379638.9
SRP19	NM_001204199.2	c.302-4513C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
REEP5	ENST00000379638.9	c.445G>A	p.Glu149Lys	missense_variant	4/5	1	NM_005669.5	P1

Frequencies

GnomAD3 genomes AF: 0.0112 AC: 1709 AN: 152142 Hom.: 8 Cov.: 32

Gnomad AFR AF: 0.00939

Gnomad AMI AF: 0.00219

Gnomad AMR AF: 0.0168

Gnomad ASJ AF: 0.0219

Gnomad EAS AF: 0.000192

Gnomad SAS AF: 0.00207

Gnomad FIN AF: 0.00179

Gnomad MID AF: 0.0380

Gnomad NFE AF: 0.0134

Gnomad OTH AF: 0.0144

GnomAD3 exomes AF: 0.00985 AC: 2466 AN: 250430 Hom.: 22 AF XY: 0.00991 AC XY: 1342 AN XY: 135476

Gnomad AFR exome AF: 0.00855

Gnomad AMR exome AF: 0.0106

Gnomad ASJ exome AF: 0.0221

Gnomad EAS exome AF: 0.0000544

Gnomad SAS exome AF: 0.00238

Gnomad FIN exome AF: 0.00180

Gnomad NFE exome AF: 0.0136

Gnomad OTH exome AF: 0.0147

GnomAD4 exome AF: 0.0127 AC: 18515 AN: 1461304 Hom.: 167 Cov.: 31 AF XY: 0.0123 AC XY: 8959 AN XY: 726970

Gnomad4 AFR exome AF: 0.00950

Gnomad4 AMR exome AF: 0.0114

Gnomad4 ASJ exome AF: 0.0227

Gnomad4 EAS exome AF: 0.0000252

Gnomad4 SAS exome AF: 0.00225

Gnomad4 FIN exome AF: 0.00183

Gnomad4 NFE exome AF: 0.0143

Gnomad4 OTH exome AF: 0.0127

GnomAD4 genome AF: 0.0112 AC: 1711 AN: 152260 Hom.: 8 Cov.: 32 AF XY: 0.0110 AC XY: 817 AN XY: 74428

Gnomad4 AFR AF: 0.00946

Gnomad4 AMR AF: 0.0167

Gnomad4 ASJ AF: 0.0219

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.00207

Gnomad4 FIN AF: 0.00179

Gnomad4 NFE AF: 0.0134

Gnomad4 OTH AF: 0.0137

Alfa AF: 0.0137 Hom.: 27

Bravo AF: 0.0124

TwinsUK AF: 0.0119 AC: 44

ALSPAC AF: 0.0135 AC: 52

ESP6500AA AF: 0.00886 AC: 39

ESP6500EA AF: 0.0136 AC: 117

ExAC AF: 0.00955 AC: 1160

Asia WGS AF: 0.00231 AC: 9 AN: 3478

EpiCase AF: 0.0141

EpiControl AF: 0.0154

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Jan 01, 2023

REEP5: BS1, BS2; SRP19: BS1, BS2 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.40
BayesDel_addAF	Benign	-0.39	T
BayesDel_noAF	Benign	-0.33
Cadd	Benign	23
Dann	Uncertain	1.0
DEOGEN2	Benign	0.31	T;T
Eigen	Uncertain	0.22
Eigen_PC	Uncertain	0.28
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Uncertain	0.97	D;D
MetaRNN	Benign	0.0070	T;T
MetaSVM	Benign	-0.83	T
MutationAssessor	Uncertain	2.9	M;.
MutationTaster	Benign	1.0	D;D;D;D
PrimateAI	Uncertain	0.55	T
PROVEAN	Benign	-2.2	N;N
REVEL	Benign	0.17
Sift	Uncertain	0.025	D;D
Sift4G	Uncertain	0.031	D;.
Polyphen		0.30	B;.
Vest4		0.64
MVP		0.59
MPC		0.34
ClinPred		0.046	T
GERP RS		3.7
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.42
gMVP		0.89

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: rs34083474; hg19: chr5-112222787; COSMIC: COSV99810178; COSMIC: COSV99810178;