rs1943161245

Variant names:

• chr12-49295390-C-G
• rs1943161245
• NM_006262.4:c.190C>G

Your query was ambiguous. Multiple possible variants found:

• chr12-49295390-C-G
• chr12-49295390-C-T

Variant summary

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

The NM_006262.4(PRPH):​c.190C>G​(p.Arg64Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000138 in 1,453,706 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict 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: 33)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: PRPH NM_006262.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.374
• 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: 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=0.15518099).

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.190C>G	p.Arg64Gly	missense	Exon 1 of 9	NP_006253.2
	TROAP-AS1	NR_120449.1		n.2682G>C		non_coding_transcript_exon	Exon 6 of 8

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PRPH	ENST00000257860.9	TSL:1 MANE Select	c.190C>G	p.Arg64Gly	missense	Exon 1 of 9	ENSP00000257860.4	P41219-1
	PRPH	ENST00000451891.4	TSL:5	c.-54C>G		5_prime_UTR	Exon 1 of 6	ENSP00000408897.4	F8W835
	TROAP-AS1	ENST00000553259.1	TSL:2	n.2682G>C		non_coding_transcript_exon	Exon 6 of 8

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000138 AC: 2 AN: 1453706 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 722630

African (AFR) AF: 0.00 AC: 0 AN: 33372

American (AMR) AF: 0.00 AC: 0 AN: 43924

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25876

East Asian (EAS) AF: 0.0000507 AC: 2 AN: 39426

South Asian (SAS) AF: 0.00 AC: 0 AN: 85184

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 50930

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5726

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1109246

Other (OTH) AF: 0.00 AC: 0 AN: 60022

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.083
BayesDel_addAF	Benign	-0.028	T
BayesDel_noAF	Benign	-0.28
CADD	Benign	18
DANN	Benign	0.95
DEOGEN2	Benign	0.25	T
Eigen	Benign	-0.67
Eigen_PC	Benign	-0.64
FATHMM_MKL	Benign	0.23	N
LIST_S2	Benign	0.67	T
M_CAP	Benign	0.072	D
MetaRNN	Benign	0.16	T
MetaSVM	Benign	-0.78	T
MutationAssessor	Uncertain	2.4	M
PhyloP100		0.37
PrimateAI	Pathogenic	0.83	D
PROVEAN	Benign	-1.1	N
REVEL	Benign	0.18
Sift	Benign	0.21	T
Sift4G	Benign	0.18	T
Polyphen		0.0030	B
Vest4		0.26
MutPred		0.51		Gain of catalytic residue at R64 (P = 3e-04)
MVP		0.61
MPC		0.72
ClinPred		0.25	T
GERP RS		3.7
PromoterAI		0.022	Neutral
Varity_R		0.16
gMVP		0.74
Mutation Taster		=78/22	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: rs1943161245; hg19: chr12-49689173;