NM_001034850.3:c.*65_*71delAAAAAAA

Variant names:

• chr5-16474669-CTTTTTTT-C
• rs200951949
• NM_001034850.3:c.*65_*71delAAAAAAA

Variant summary

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

The NM_001034850.3(RETREG1):​c.*65_*71delAAAAAAA variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000882 in 1,133,264 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 0)
  • Exomes 𝑓: 8.8e-7 (0 hom.)
• Consequence: RETREG1 NM_001034850.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.982
• 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 Gene-Disease associations (from GenCC):

• hereditary sensory and autonomic neuropathy

  Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
• neuropathy, hereditary sensory and autonomic, type 2B

  Inheritance: AR Classification: DEFINITIVE Submitted by: G2P
• hereditary sensory and autonomic neuropathy type 2

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ENSG00000289112 (HGNC:):

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.*65_*71delAAAAAAA		3_prime_UTR	Exon 9 of 9	NP_001030022.1	Q9H6L5-1
	RETREG1	NM_019000.5		c.*65_*71delAAAAAAA		3_prime_UTR	Exon 7 of 7	NP_061873.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RETREG1	ENST00000306320.10	TSL:1 MANE Select	c.*65_*71delAAAAAAA		3_prime_UTR	Exon 9 of 9	ENSP00000304642.9	Q9H6L5-1
	RETREG1	ENST00000399793.6	TSL:1	c.*65_*71delAAAAAAA		3_prime_UTR	Exon 7 of 7	ENSP00000382691.2	Q9H6L5-2
	RETREG1	ENST00000510362.6	TSL:1	n.*65_*71delAAAAAAA		non_coding_transcript_exon	Exon 7 of 8	ENSP00000425089.2	H0Y9U4

Frequencies

GnomAD3 genomes Cov.: 0

GnomAD4 exome AF: 8.82e-7 AC: 1 AN: 1133264 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 568544

African (AFR) AF: 0.00 AC: 0 AN: 24972

American (AMR) AF: 0.00 AC: 0 AN: 26008

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 20182

East Asian (EAS) AF: 0.00 AC: 0 AN: 34312

South Asian (SAS) AF: 0.00 AC: 0 AN: 63662

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 35868

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4554

European-Non Finnish (NFE) AF: 0.00000114 AC: 1 AN: 875664

Other (OTH) AF: 0.00 AC: 0 AN: 48042

GnomAD4 genome Cov.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.98

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs200951949; hg19: chr5-16474778;