12-49295178-G-C

Variant names:

• chr12-49295178-G-C
• rs267607670
• NM_006262.4:c.-23G>C

Variant summary

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

The NM_006262.4(PRPH):​c.-23G>C variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as not provided (no stars).

• Frequency: Genomes: not found (cov: 33)
• Consequence: PRPH NM_006262.4 5_prime_UTR_premature_start_codon_gain
• Clinical Significance: not provided no classification provided O:1
• Conservation: PhyloP100: -0.458
• Publications: 0 publications found

Genes affected

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]

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

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=-0.74).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006262.4. 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
	PRPH	NM_006262.4	MANE Select	c.-23G>C		5_prime_UTR_premature_start_codon_gain	Exon 1 of 9	NP_006253.2
	PRPH	NM_006262.4	MANE Select	c.-23G>C		5_prime_UTR	Exon 1 of 9	NP_006253.2
	TROAP-AS1	NR_120449.1		n.2812+82C>G		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PRPH	ENST00000257860.9	TSL:1 MANE Select	c.-23G>C		5_prime_UTR_premature_start_codon_gain	Exon 1 of 9	ENSP00000257860.4	P41219-1
	PRPH	ENST00000257860.9	TSL:1 MANE Select	c.-23G>C		5_prime_UTR	Exon 1 of 9	ENSP00000257860.4	P41219-1
	TROAP-AS1	ENST00000553259.1	TSL:2	n.2812+82C>G		intron	N/A

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

ClinVar

ClinVar submissions

Significance: not provided

Revision: no classification provided

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.74
CADD	Benign	12
DANN	Benign	0.87
PhyloP100		-0.46
PromoterAI		-0.0028	Neutral

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: rs267607670; hg19: chr12-49688961;