NM_002768.5:c.*57C>T

Variant names:

• chr16-89646009-G-A
• rs768288651
• NM_002768.5:c.*57C>T

Variant summary

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

The NM_002768.5(CHMP1A):​c.*57C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000412 in 1,457,734 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000041 (0 hom.)
• Consequence: CHMP1A NM_002768.5 3_prime_UTR
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.221
• Publications: 0 publications found

Genes affected

CHMP1A (HGNC:8740): (charged multivesicular body protein 1A) This gene encodes a member of the CHMP/Chmp family of proteins which are involved in multivesicular body sorting of proteins to the interiors of lysosomes. The initial prediction of the protein sequence encoded by this gene suggested that the encoded protein was a metallopeptidase. The nomenclature has been updated recently to reflect the correct biological function of this encoded protein. Several transcripts encoding different isoforms have been found for this gene. [provided by RefSeq, Dec 2012]

CHMP1A Gene-Disease associations (from GenCC):

• pontocerebellar hypoplasia type 8

  Inheritance: AR Classification: STRONG, SUPPORTIVE Submitted by: G2P, Labcorp Genetics (formerly Invitae), Orphanet

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 (REVEL=0.125).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002768.5. 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
	CHMP1A	NM_002768.5	MANE Select	c.*57C>T		3_prime_UTR	Exon 7 of 7	NP_002759.2	Q9HD42-1
	CHMP1A	NM_001083314.4		c.628C>T	p.Pro210Ser	missense	Exon 6 of 6	NP_001076783.1
	CHMP1A	NR_046418.3		n.936C>T		non_coding_transcript_exon	Exon 7 of 7

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CHMP1A	ENST00000397901.8	TSL:1 MANE Select	c.*57C>T		3_prime_UTR	Exon 7 of 7	ENSP00000380998.3	Q9HD42-1
	CHMP1A	ENST00000547687.2	TSL:1	n.1396C>T		non_coding_transcript_exon	Exon 2 of 2
	CHMP1A	ENST00000675536.1		c.703C>T	p.Pro235Ser	missense	Exon 7 of 7	ENSP00000501759.1	A0A6Q8PFF8

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD2 exomes AF: 0.00000410 AC: 1 AN: 243632 AF XY: 0.00000753

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000907

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000412 AC: 6 AN: 1457734 Hom.: 0 Cov.: 31 AF XY: 0.00000414 AC XY: 3 AN XY: 725248

African (AFR) AF: 0.00 AC: 0 AN: 33282

American (AMR) AF: 0.00 AC: 0 AN: 43880

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25978

East Asian (EAS) AF: 0.00 AC: 0 AN: 39642

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

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52770

Middle Eastern (MID) AF: 0.000180 AC: 1 AN: 5552

European-Non Finnish (NFE) AF: 0.00000360 AC: 4 AN: 1110654

Other (OTH) AF: 0.0000166 AC: 1 AN: 60190

GnomAD4 genome Cov.: 33

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	Inborn genetic diseases (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.76
CADD	Benign	3.7
DANN	Benign	0.68
PhyloP100		0.22

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: rs768288651; hg19: chr16-89712417;