rs1326167901

Variant names:

• chr5-16616874-G-A
• rs1326167901
• NM_001034850.3:c.98C>T

Your query was ambiguous. Multiple possible variants found:

• chr5-16616874-G-A
• chr5-16616874-G-T
• chr5-16616874-G-C

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001034850.3(RETREG1):​c.98C>T​(p.Ser33Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000802 in 1,496,054 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. S33Y) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.0000066 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0000082 (0 hom.)
• Consequence: RETREG1 NM_001034850.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.88
• Publications: 0 publications found

Genes affected

RETREG1 (HGNC:25964): (reticulophagy regulator 1) The protein encoded by this gene is a cis-Golgi transmembrane protein that may be necessary for the long-term survival of nociceptive and autonomic ganglion neurons. Mutations in this gene are a cause of hereditary sensory and autonomic neuropathy type IIB (HSAN IIB), and this gene may also play a role in susceptibility to vascular dementia. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene. [provided by RefSeq, Nov 2011]

RETREG1-AS1 (HGNC:55551): (RETREG1 antisense RNA 1)

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.09366658).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001034850.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RETREG1	NM_001034850.3	MANE Select	c.98C>T	p.Ser33Phe	missense	Exon 1 of 9	NP_001030022.1	Q9H6L5-1
	RETREG1-AS1	NR_109946.1		n.561+388G>A		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RETREG1	ENST00000306320.10	TSL:1 MANE Select	c.98C>T	p.Ser33Phe	missense	Exon 1 of 9	ENSP00000304642.9	Q9H6L5-1
	RETREG1	ENST00000682229.1		c.98C>T	p.Ser33Phe	missense	Exon 1 of 10	ENSP00000507342.1	A0A804HJ37
	RETREG1	ENST00000682564.1		c.98C>T	p.Ser33Phe	missense	Exon 1 of 9	ENSP00000508099.1	A0A804HKW5

Frequencies

GnomAD3 genomes AF: 0.00000658 AC: 1 AN: 152072 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.00000818 AC: 11 AN: 1343982 Hom.: 0 Cov.: 29 AF XY: 0.00000755 AC XY: 5 AN XY: 662650

African (AFR) AF: 0.00 AC: 0 AN: 27138

American (AMR) AF: 0.00 AC: 0 AN: 30912

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 23806

East Asian (EAS) AF: 0.00 AC: 0 AN: 30940

South Asian (SAS) AF: 0.00 AC: 0 AN: 75310

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 33252

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4232

European-Non Finnish (NFE) AF: 0.00000941 AC: 10 AN: 1062470

Other (OTH) AF: 0.0000179 AC: 1 AN: 55922

GnomAD4 genome AF: 0.00000658 AC: 1 AN: 152072 Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1 AN XY: 74288

African (AFR) AF: 0.00 AC: 0 AN: 41452

American (AMR) AF: 0.00 AC: 0 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5166

South Asian (SAS) AF: 0.00 AC: 0 AN: 4838

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10574

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 314

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 67984

Other (OTH) AF: 0.00 AC: 0 AN: 2088

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000113

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.22	T
BayesDel_noAF	Benign	-0.56
CADD	Benign	15
DANN	Benign	0.74
DEOGEN2	Benign	0.0079	T
Eigen	Benign	-1.0
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.078	N
LIST_S2	Benign	0.33	T
M_CAP	Benign	0.0088	T
MetaRNN	Benign	0.094	T
MetaSVM	Benign	-1.0	T
PhyloP100		1.9
PrimateAI	Uncertain	0.68	T
PROVEAN	Benign	-0.73	N
REVEL	Benign	0.084
Sift	Benign	0.041	D
Sift4G	Benign	0.083	T
Polyphen		0.023	B
Vest4		0.16
MutPred		0.17		Loss of phosphorylation at S33 (P = 0.0037)
MVP		0.40
MPC		0.36
ClinPred		0.14	T
GERP RS		1.4
PromoterAI		0.10	Neutral
Varity_R		0.067
gMVP		0.17
Mutation Taster		=96/4	polymorphism

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: rs1326167901; hg19: chr5-16616983;