Genetic Variant CHMP1A:p.Asn196Ser (chr16-89646070-T-C) – ACMG Classification: Uncertain_significance (1 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2BP4

The NM_002768.5(CHMP1A):c.587A>G(p.Asn196Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000713 in 1,402,846 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: 7.1e-7 ( 0 hom. )

Consequence

CHMP1A
NM_002768.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.79

Publications

0 publications found

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]

CHMP1A Gene-Disease associations (from GenCC):

pontocerebellar hypoplasia type 8
Inheritance: AR Classification: STRONG, SUPPORTIVE Submitted by: G2P, Labcorp Genetics (formerly Invitae), Orphanet

CHMP1A links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.32200304).

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

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
CHMP1A	NM_002768.5	MANE Select	c.587A>G	p.Asn196Ser	missense	Exon 7 of 7	NP_002759.2	Q9HD42-1
CHMP1A	NM_001083314.4		c.567A>G	p.Glu189Glu	synonymous	Exon 6 of 6	NP_001076783.1
CHMP1A	NR_046418.3		n.875A>G		non_coding_transcript_exon	Exon 7 of 7

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
CHMP1A	ENST00000397901.8	TSL:1 MANE Select	c.587A>G	p.Asn196Ser	missense	Exon 7 of 7	ENSP00000380998.3	Q9HD42-1
CHMP1A	ENST00000547687.2	TSL:1	n.1335A>G		non_coding_transcript_exon	Exon 2 of 2
CHMP1A	ENST00000676355.1		c.596A>G	p.Asn199Ser	missense	Exon 8 of 8	ENSP00000502147.1	A0A6Q8PG85

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

7.13e-7

AC:

AN:

1402846

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

692016

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

31460

American (AMR)

AF:

0.00

AC:

AN:

35896

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

22788

East Asian (EAS)

AF:

0.00

AC:

AN:

38176

South Asian (SAS)

AF:

0.00

AC:

AN:

77858

European-Finnish (FIN)

AF:

0.00

AC:

AN:

51060

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4646

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1083310

Other (OTH)

AF:

0.0000173

AC:

AN:

57652

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ExAC

AF:

0.00000829

AC:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

Inborn genetic diseases (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.15

BayesDel_addAF

Pathogenic

0.21

BayesDel_noAF

Uncertain

0.060

CADD

Benign

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.0084

Eigen

Uncertain

0.40

Eigen_PC

Uncertain

0.39

FATHMM_MKL

Benign

0.71

LIST_S2

Uncertain

0.91

M_CAP

Pathogenic

0.61

MetaRNN

Benign

0.32

MetaSVM

Uncertain

0.43

MutationAssessor

Benign

1.2

PhyloP100

1.8

PrimateAI

Uncertain

0.64

PROVEAN

Benign

-1.7

REVEL

Uncertain

0.40

Sift

Benign

0.11

Sift4G

Benign

0.30

Polyphen

1.0

Vest4

0.29

MutPred

0.30

Gain of phosphorylation at N196 (P = 0.0056)

MVP

0.85

MPC

0.48

ClinPred

0.49

GERP RS

5.5

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.6

Varity_R

0.12

gMVP

0.20

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over