Variant 16-89646070-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 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

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 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
CHMP1A	NM_002768.5 linkuse as main transcript	c.587A>G	p.Asn196Ser	missense_variant	7/7	ENST00000397901.8	NP_002759.2
CHMP1A	XM_047434195.1 linkuse as main transcript	c.395A>G	p.Asn132Ser	missense_variant	7/7		XP_047290151.1
CHMP1A	NM_001083314.4 linkuse as main transcript	c.567A>G	p.Glu189=	synonymous_variant	6/6		NP_001076783.1
CHMP1A	NR_046418.3 linkuse as main transcript	n.875A>G		non_coding_transcript_exon_variant	7/7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CHMP1A	ENST00000397901.8 linkuse as main transcript	c.587A>G	p.Asn196Ser	missense_variant	7/7	1	NM_002768.5	ENSP00000380998	P1	Q9HD42-1

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

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.0000173

GnomAD4 genome

Cov.:

ExAC

AF:

0.00000829

AC:

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 submitter

clinical testing

Ambry Genetics

Sep 09, 2021

The c.587A>G (p.N196S) alteration is located in exon 7 (coding exon 7) of the CHMP1A gene. This alteration results from a A to G substitution at nucleotide position 587, causing the asparagine (N) at amino acid position 196 to be replaced by a serine (S). 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

AlphaMissense

Benign

0.15

BayesDel_addAF

Pathogenic

0.21

BayesDel_noAF

Uncertain

0.060

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.0084

T;.;.

Eigen

Uncertain

0.40

Eigen_PC

Uncertain

0.39

FATHMM_MKL

Benign

0.71

LIST_S2

Uncertain

0.91

D;D;D

M_CAP

Pathogenic

0.61

MetaRNN

Benign

0.32

T;T;T

MetaSVM

Uncertain

0.43

MutationAssessor

Benign

1.2

L;.;.

MutationTaster

Benign

1.0

D;D;D;D

PrimateAI

Uncertain

0.64

PROVEAN

Benign

-1.7

N;N;N

REVEL

Uncertain

0.40

Sift

Benign

0.11

T;D;T

Sift4G

Benign

0.30

T;T;T

Polyphen

1.0

D;.;.

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

LitVar

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

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over