12-49295097-C-T

Variant names:

• chr12-49295097-C-T
• rs115335961
• ENST00000553259.1:n.2812+163G>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The ENST00000553259.1(TROAP-AS1):​n.2812+163G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000835 in 1,197,122 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 32)
  • Exomes 𝑓: 8.4e-7 (0 hom.)
• Consequence: TROAP-AS1 ENST00000553259.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.18
• Publications: 0 publications found

Genes affected

TROAP-AS1 (HGNC:55453): (TROAP and PRPH antisense RNA 1)

PRPH (HGNC:9461): (peripherin) This gene encodes a cytoskeletal protein found in neurons of the peripheral nervous system. The encoded protein is a type III intermediate filament protein with homology to other cytoskeletal proteins such as desmin, and is a different protein that the peripherin found in photoreceptors. Mutations in this gene have been associated with susceptibility to amyotrophic lateral sclerosis. [provided by RefSeq, Jul 2008]

PRPH Gene-Disease associations (from GenCC):

• amyotrophic lateral sclerosis

  Inheritance: AD Classification: LIMITED Submitted by: ClinGen
• amyotrophic lateral sclerosis type 1

  Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.61).

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000553259.1. 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
	TROAP-AS1	NR_120449.1		n.2812+163G>A		intron	N/A
	PRPH	NM_006262.4	MANE Select	c.-104C>T		upstream_gene	N/A	NP_006253.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TROAP-AS1	ENST00000553259.1	TSL:2	n.2812+163G>A		intron	N/A
	TROAP-AS1	ENST00000797029.1		n.269-6734G>A		intron	N/A
	TROAP-AS1	ENST00000797030.1		n.358-6734G>A		intron	N/A

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 8.35e-7 AC: 1 AN: 1197122 Hom.: 0 Cov.: 18 AF XY: 0.00000168 AC XY: 1 AN XY: 595538

African (AFR) AF: 0.00 AC: 0 AN: 27922

American (AMR) AF: 0.00 AC: 0 AN: 33676

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 22426

East Asian (EAS) AF: 0.00 AC: 0 AN: 34652

South Asian (SAS) AF: 0.0000137 AC: 1 AN: 73032

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 35342

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5024

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 913872

Other (OTH) AF: 0.00 AC: 0 AN: 51176

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.61
CADD	Benign	17
DANN	Benign	0.90
PhyloP100		2.2

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: rs115335961; hg19: chr12-49688880;