1-152155462-T-C

Variant names:

• chr1-152155462-T-C
• NM_001122965.1:c.1637A>G

Variant summary

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

The NM_001122965.1(RPTN):​c.1637A>G​(p.His546Arg) variant causes a missense 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. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. H546P) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: RPTN NM_001122965.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -2.35
• Publications: 0 publications found

Genes affected

RPTN (HGNC:26809): (repetin) Predicted to enable calcium ion binding activity and transition metal ion binding activity. Predicted to be located in cytosol. Predicted to be active in cornified envelope. [provided by Alliance of Genome Resources, Apr 2022]

ENSG00000293250 (HGNC:):

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 (MetaRNN=0.05793777).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001122965.1. 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
	RPTN	NM_001122965.1	MANE Select	c.1637A>G	p.His546Arg	missense	Exon 3 of 3	NP_001116437.1	Q6XPR3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RPTN	ENST00000316073.3	TSL:1 MANE Select	c.1637A>G	p.His546Arg	missense	Exon 3 of 3	ENSP00000317895.3	Q6XPR3
	ENSG00000293250	ENST00000628080.1	TSL:5	n.48-30757A>G		intron	N/A

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 6.85e-7 AC: 1 AN: 1459242 Hom.: 0 Cov.: 32 AF XY: 0.00000138 AC XY: 1 AN XY: 725814

African (AFR) AF: 0.00 AC: 0 AN: 33386

American (AMR) AF: 0.00 AC: 0 AN: 44224

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26082

East Asian (EAS) AF: 0.00 AC: 0 AN: 39530

South Asian (SAS) AF: 0.00 AC: 0 AN: 85786

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53382

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 9.00e-7 AC: 1 AN: 1110774

Other (OTH) AF: 0.00 AC: 0 AN: 60310

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.095
BayesDel_addAF	Benign	-0.38	T
BayesDel_noAF	Benign	-0.78
CADD	Benign	1.6
DANN	Benign	0.45
DEOGEN2	Benign	0.057	T
Eigen	Benign	-0.94
Eigen_PC	Benign	-1.0
FATHMM_MKL	Benign	0.036	N
LIST_S2	Benign	0.38	T
M_CAP	Benign	0.0016	T
MetaRNN	Benign	0.058	T
MetaSVM	Benign	-0.94	T
MutationAssessor	Uncertain	2.9	M
PhyloP100		-2.4
PrimateAI	Benign	0.22	T
PROVEAN	Benign	-2.1	N
REVEL	Benign	0.037
Sift	Benign	0.32	T
Sift4G	Benign	0.51	T
Polyphen		0.0090	B
Vest4		0.066
MutPred		0.21		Gain of MoRF binding (P = 0.0116)
MVP		0.22
MPC		0.052
ClinPred		0.095	T
GERP RS		0.76
Varity_R		0.043
gMVP		0.033
Mutation Taster		=94/6	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

hg19: chr1-152127938;