5-16616689-T-G

Variant names:

• chr5-16616689-T-G
• NM_001034850.3:c.283A>C
• RETREG1 p.Ser95Arg

Variant summary

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

The NM_001034850.3(RETREG1):​c.283A>C​(p.Ser95Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: RETREG1 NM_001034850.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.19
• 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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

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.283A>C	p.Ser95Arg	missense	Exon 1 of 9	NP_001030022.1	Q9H6L5-1
	RETREG1-AS1	NR_109946.1		n.561+203T>G		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RETREG1	ENST00000306320.10	TSL:1 MANE Select	c.283A>C	p.Ser95Arg	missense	Exon 1 of 9	ENSP00000304642.9	Q9H6L5-1
	RETREG1	ENST00000682229.1		c.283A>C	p.Ser95Arg	missense	Exon 1 of 10	ENSP00000507342.1	A0A804HJ37
	RETREG1	ENST00000682564.1		c.283A>C	p.Ser95Arg	missense	Exon 1 of 9	ENSP00000508099.1	A0A804HKW5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 29

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.95
BayesDel_addAF	Uncertain	0.10	D
BayesDel_noAF	Benign	-0.090
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Benign	0.17	T
Eigen	Benign	0.10
Eigen_PC	Benign	0.098
FATHMM_MKL	Benign	0.65	D
LIST_S2	Benign	0.57	T
M_CAP	Pathogenic	0.48	D
MetaRNN	Uncertain	0.67	D
MetaSVM	Benign	-0.86	T
PhyloP100		2.2
PrimateAI	Uncertain	0.77	T
PROVEAN	Uncertain	-2.8	D
REVEL	Benign	0.28
Sift	Uncertain	0.0020	D
Sift4G	Uncertain	0.0050	D
PromoterAI		0.019	Neutral
Varity_R		0.38
gMVP		0.85
Mutation Taster		=85/15	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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr5-16616798;