16-89646688-G-A

Position:

chr16-89646688-G-A

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6BP7

The NM_002768.5(CHMP1A):c.408C>T(p.Ala136=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000336 in 1,610,236 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 Conflicting classifications of pathogenicity (no stars).

Frequency

Genomes: 𝑓 0.00044 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00033 ( 0 hom. )

Consequence

CHMP1A
NM_002768.5 synonymous

Scores

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1B:3

Conservation

PhyloP100: 0.838

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.47).

BP6

Variant 16-89646688-G-A is Benign according to our data. Variant chr16-89646688-G-A is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 390042.We mark this variant Likely_benign, oryginal submissions are: {Likely_benign=3, Uncertain_significance=1}.

BP7

Synonymous conserved (PhyloP=0.838 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
CHMP1A	NM_002768.5 linkuse as main transcript	c.408C>T	p.Ala136=	synonymous_variant	6/7	ENST00000397901.8	NP_002759.2
CHMP1A	NM_001083314.4 linkuse as main transcript	c.388C>T	p.His130Tyr	missense_variant	5/6		NP_001076783.1
CHMP1A	XM_047434195.1 linkuse as main transcript	c.216C>T	p.Ala72=	synonymous_variant	6/7		XP_047290151.1
CHMP1A	NR_046418.3 linkuse as main transcript	n.696C>T		non_coding_transcript_exon_variant	6/7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CHMP1A	ENST00000397901.8 linkuse as main transcript	c.408C>T	p.Ala136=	synonymous_variant	6/7	1	NM_002768.5	ENSP00000380998	P1	Q9HD42-1

Frequencies

GnomAD3 genomes

AF:

0.000440

AC:

AN:

152188

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000314

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.000288

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000471

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000661

Gnomad OTH

AF:

0.00143

GnomAD3 exomes

AF:

0.000320

AC:

AN:

240492

Hom.:

AF XY:

0.000290

AC XY:

AN XY:

131174

show subpopulations

Gnomad AFR exome

AF:

0.000347

Gnomad AMR exome

AF:

0.000147

Gnomad ASJ exome

AF:

0.000204

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000241

Gnomad NFE exome

AF:

0.000544

Gnomad OTH exome

AF:

0.000171

GnomAD4 exome

AF:

0.000325

AC:

474

AN:

1458048

Hom.:

Cov.:

AF XY:

0.000321

AC XY:

233

AN XY:

724954

show subpopulations

Gnomad4 AFR exome

AF:

0.000239

Gnomad4 AMR exome

AF:

0.000203

Gnomad4 ASJ exome

AF:

0.000192

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.000211

Gnomad4 NFE exome

AF:

0.000387

Gnomad4 OTH exome

AF:

0.000183

GnomAD4 genome

AF:

0.000440

AC:

AN:

152188

Hom.:

Cov.:

AF XY:

0.000471

AC XY:

AN XY:

74336

show subpopulations

Gnomad4 AFR

AF:

0.000314

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.000288

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.000471

Gnomad4 NFE

AF:

0.000661

Gnomad4 OTH

AF:

0.00143

Alfa

AF:

0.000479

Hom.:

Bravo

AF:

0.000385

ClinVar

Significance: Conflicting classifications of pathogenicity

Submissions summary: Uncertain:1Benign:3

Revision: criteria provided, conflicting classifications

LINK: link

Submissions by phenotype

not provided

Benign:2

Likely benign, criteria provided, single submitter	clinical testing	GeneDx	Nov 03, 2019	- -
Likely benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 01, 2024	- -

Inborn genetic diseases

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jan 26, 2022

The c.388C>T (p.H130Y) alteration is located in exon 5 (coding exon 5) of the CHMP1A gene. This alteration results from a C to T substitution at nucleotide position 388, causing the histidine (H) at amino acid position 130 to be replaced by a tyrosine (Y). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Genetic Services Laboratory, University of Chicago

Jan 27, 2017

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.47

CADD

Benign

DANN

Benign

0.88

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

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.

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