19-6361727-G-T

Variant names:

• chr19-6361727-G-T
• NM_006012.4:c.153G>T
• CLPP p.Thr51Thr

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP7

The NM_006012.4(CLPP):​c.153G>T​(p.Thr51Thr) variant causes a synonymous 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. T51T) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: CLPP NM_006012.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0710
• Publications: 0 publications found

Genes affected

CLPP (HGNC:2084): (caseinolytic mitochondrial matrix peptidase proteolytic subunit) The protein encoded by this gene belongs to the peptidase family S14 and hydrolyzes proteins into small peptides in the presence of ATP and magnesium. The protein is transported into mitochondrial matrix and is associated with the inner mitochondrial membrane. [provided by RefSeq, Jul 2008]

CLPP Gene-Disease associations (from GenCC):

• Perrault syndrome 3

  Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), G2P, ClinGen
• Perrault syndrome

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ENSG00000269802 (HGNC:):

ACMG classification

Our verdict: Likely_benign. The variant received -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.75).
• BP7: Synonymous conserved (PhyloP=-0.071 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006012.4. 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
	CLPP	NM_006012.4	MANE Select	c.153G>T	p.Thr51Thr	synonymous	Exon 1 of 6	NP_006003.1	Q16740

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CLPP	ENST00000245816.11	TSL:1 MANE Select	c.153G>T	p.Thr51Thr	synonymous	Exon 1 of 6	ENSP00000245816.3	Q16740
	CLPP	ENST00000715787.1		c.153G>T	p.Thr51Thr	synonymous	Exon 1 of 6	ENSP00000520519.1	Q16740
	CLPP	ENST00000926271.1		c.153G>T	p.Thr51Thr	synonymous	Exon 1 of 5	ENSP00000596330.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1354944 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 665262

African (AFR) AF: 0.00 AC: 0 AN: 30856

American (AMR) AF: 0.00 AC: 0 AN: 32534

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 22740

East Asian (EAS) AF: 0.00 AC: 0 AN: 35546

South Asian (SAS) AF: 0.00 AC: 0 AN: 74502

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 33020

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5490

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1063720

Other (OTH) AF: 0.00 AC: 0 AN: 56536

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.75
CADD	Benign	7.1
DANN	Benign	0.74
PhyloP100		-0.071
PromoterAI		-0.035	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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr19-6361738;