9-33270481-A-T

Variant names:

• chr9-33270481-A-T
• rs844239
• NM_016410.6:c.222-142A>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_016410.6(CHMP5):​c.222-142A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: CHMP5 NM_016410.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.967
• Publications: 7 publications found

Genes affected

CHMP5 (HGNC:26942): (charged multivesicular body protein 5) CHMP5 belongs to the chromatin-modifying protein/charged multivesicular body protein (CHMP) family. These proteins are components of ESCRT-III (endosomal sorting complex required for transport III), a complex involved in degradation of surface receptor proteins and formation of endocytic multivesicular bodies (MVBs). Some CHMPs have both nuclear and cytoplasmic/vesicular distributions, and one such CHMP, CHMP1A (MIM 164010), is required for both MVB formation and regulation of cell cycle progression (Tsang et al., 2006 [PubMed 16730941]).[supplied by OMIM, Mar 2008]

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CHMP5	NM_016410.6	c.222-142A>T		intron_variant	Intron 3 of 7	ENST00000223500.9	NP_057494.3
CHMP5	NM_001195536.2	c.222-142A>T		intron_variant	Intron 3 of 6		NP_001182465.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CHMP5	ENST00000223500.9	c.222-142A>T		intron_variant	Intron 3 of 7	1	NM_016410.6	ENSP00000223500.7
CHMP5	ENST00000419016.6	c.222-142A>T		intron_variant	Intron 3 of 6	2		ENSP00000442725.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 491940 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 259940

African (AFR) AF: 0.00 AC: 0 AN: 12496

American (AMR) AF: 0.00 AC: 0 AN: 17062

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 13866

East Asian (EAS) AF: 0.00 AC: 0 AN: 30608

South Asian (SAS) AF: 0.00 AC: 0 AN: 45124

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 40702

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2200

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 302924

Other (OTH) AF: 0.00 AC: 0 AN: 26958

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 4444

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	0.0090
DANN	Benign	0.77
PhyloP100		-0.97

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: rs844239; hg19: chr9-33270479;