16-89645957-G-A

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_002768.5(CHMP1A):​c.*109C>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 0.000175 in 1,611,016 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: 𝑓 0.00020 ( 0 hom., cov: 33)
Exomes 𝑓: 0.00017 ( 0 hom. )

Consequence

CHMP1A
NM_002768.5 3_prime_UTR

Scores

2

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.0280
Variant links:
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.79).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
CHMP1ANM_002768.5 linkuse as main transcriptc.*109C>T 3_prime_UTR_variant 7/7 ENST00000397901.8 NP_002759.2
CHMP1ANM_001083314.4 linkuse as main transcriptc.680C>T p.Ala227Val missense_variant 6/6 NP_001076783.1
CHMP1AXM_047434195.1 linkuse as main transcriptc.*109C>T 3_prime_UTR_variant 7/7 XP_047290151.1
CHMP1ANR_046418.3 linkuse as main transcriptn.988C>T non_coding_transcript_exon_variant 7/7

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
CHMP1AENST00000397901.8 linkuse as main transcriptc.*109C>T 3_prime_UTR_variant 7/71 NM_002768.5 ENSP00000380998 P1Q9HD42-1

Frequencies

GnomAD3 genomes
AF:
0.000210
AC:
32
AN:
152248
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.000265
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000458
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.000206
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.000115
AC:
28
AN:
242852
Hom.:
0
AF XY:
0.0000978
AC XY:
13
AN XY:
132886
show subpopulations
Gnomad AFR exome
AF:
0.000277
Gnomad AMR exome
AF:
0.000147
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.0000330
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.000164
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.000172
AC:
251
AN:
1458650
Hom.:
0
Cov.:
31
AF XY:
0.000165
AC XY:
120
AN XY:
725612
show subpopulations
Gnomad4 AFR exome
AF:
0.0000897
Gnomad4 AMR exome
AF:
0.000112
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000116
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.000207
Gnomad4 OTH exome
AF:
0.000150
GnomAD4 genome
AF:
0.000203
AC:
31
AN:
152366
Hom.:
0
Cov.:
33
AF XY:
0.000148
AC XY:
11
AN XY:
74500
show subpopulations
Gnomad4 AFR
AF:
0.000240
Gnomad4 AMR
AF:
0.000457
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.000206
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.000213
Hom.:
0
Bravo
AF:
0.000264
EpiCase
AF:
0.000109
EpiControl
AF:
0.0000595

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

Inborn genetic diseases Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingAmbry GeneticsAug 13, 2021The c.680C>T (p.A227V) alteration is located in exon 6 (coding exon 6) of the CHMP1A gene. This alteration results from a C to T substitution at nucleotide position 680, causing the alanine (A) at amino acid position 227 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.79
CADD
Benign
7.0
DANN
Benign
0.76
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.1

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.11
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs375366854; hg19: chr16-89712365; API