Genetic Variant ENST00000565988.1:n.737C>A (chr14-24213911-G-T) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The ENST00000565988.1(ENSG00000260669):n.737C>A variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000751 in 1,331,702 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: 7.5e-7 ( 0 hom. )

Consequence

ENSG00000260669
ENST00000565988.1 non_coding_transcript_exon

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.26

Publications

0 publications found

Variant links:

Genes affected

ENSG00000260669 (HGNC:):

ENSG00000260669 links:

MDP1 (HGNC:28781): (magnesium dependent phosphatase 1) Predicted to enable acid phosphatase activity. Predicted to be involved in fructosamine metabolic process and peptidyl-tyrosine dephosphorylation. [provided by Alliance of Genome Resources, Apr 2022]

MDP1 links:

NEDD8-MDP1 (HGNC:39551): (NEDD8-MDP1 readthrough) This locus represents naturally occurring read-through transcription between the neighboring NEDD8 (neural precursor cell expressed, developmentally down-regulated 8) and MDP1 (magnesium-dependent phosphatase 1) genes on chromosome 14. One of the read-through transcripts on this locus encodes a fusion protein that shares sequence identity with the products of each individual gene. [provided by RefSeq, Jul 2016]

NEDD8-MDP1 links:

CHMP4A (HGNC:20274): (charged multivesicular body protein 4A) CHMP4A 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]

CHMP4A links:

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ACMG classification

Classification was made for transcript

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=-0.64).

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000565988.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
MDP1	NM_138476.4	MANE Select	c.*113C>A	downstream_gene	N/A	NP_612485.2
NEDD8-MDP1	NM_001199823.3		c.*113C>A	downstream_gene	N/A	NP_001186752.1
MDP1	NM_001199822.2		c.*278C>A	downstream_gene	N/A	NP_001186751.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
ENSG00000260669	ENST00000565988.1	TSL:1	n.737C>A	non_coding_transcript_exon	Exon 5 of 10
ENSG00000260669	ENST00000528804.1	TSL:2	n.930C>A	non_coding_transcript_exon	Exon 4 of 4
MDP1	ENST00000288087.12	TSL:1 MANE Select	c.*113C>A	downstream_gene	N/A	ENSP00000288087.7	Q86V88-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

7.51e-7

AC:

AN:

1331702

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

650872

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

29544

American (AMR)

AF:

0.00

AC:

AN:

25524

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

19454

East Asian (EAS)

AF:

0.00

AC:

AN:

38118

South Asian (SAS)

AF:

0.00

AC:

AN:

65742

European-Finnish (FIN)

AF:

0.00

AC:

AN:

45830

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5208

European-Non Finnish (NFE)

AF:

9.55e-7

AC:

AN:

1047344

Other (OTH)

AF:

0.00

AC:

AN:

54938

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.575

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.64

CADD

Benign

5.8

(source)

DANN

Benign

0.87

PhyloP100

-1.3

PromoterAI

-0.017

Neutral

(source)

Splicing

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

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over