Genetic Variant NM_032222.3:c.115C>A (chr7-30778483-C-A) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_032222.3(MINDY4):c.115C>A(p.Leu39Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,862 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. L39F) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

MINDY4
NM_032222.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.882

Publications

0 publications found

Variant links:

Genes affected

MINDY4 (HGNC:21916): (MINDY lysine 48 deubiquitinase 4) Predicted to enable Lys48-specific deubiquitinase activity. Predicted to be involved in protein K48-linked deubiquitination. [provided by Alliance of Genome Resources, Apr 2022]

MINDY4 links:

INMT-MINDY4 (HGNC:41995): (INMT-MINDY4 readthrough (NMD candidate)) This locus represents rare but naturally occurring read-through transcription between the INMT (indolethylamine N-methyltransferase) and FAM188B (family with sequence similarity 188, member B) genes on chromosome 7. The read-through transcript is unlikely to produce a protein because it is a nonsense-mediated mRNA decay (NMD) candidate based on translation from the supported INMT start codon. [provided by RefSeq, Nov 2010]

INMT-MINDY4 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.17747292).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_032222.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MINDY4	NM_032222.3	MANE Select	c.115C>A	p.Leu39Ile	missense	Exon 2 of 18	NP_115598.2	Q4G0A6
	INMT-MINDY4	NR_037598.1		n.644C>A		non_coding_transcript_exon	Exon 4 of 20

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
MINDY4	ENST00000265299.6	TSL:1 MANE Select	c.115C>A	p.Leu39Ile	missense	Exon 2 of 18	ENSP00000265299.6	Q4G0A6
INMT-MINDY4	ENST00000458257.5	TSL:2	n.*202C>A		non_coding_transcript_exon	Exon 4 of 20	ENSP00000456039.1	F8WBC2
INMT-MINDY4	ENST00000458257.5	TSL:2	n.*202C>A		3_prime_UTR	Exon 4 of 20	ENSP00000456039.1	F8WBC2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461862

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

727232

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33480

American (AMR)

AF:

0.00

AC:

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26134

East Asian (EAS)

AF:

0.00

AC:

AN:

39700

South Asian (SAS)

AF:

0.0000116

AC:

AN:

86258

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53420

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1111982

Other (OTH)

AF:

0.00

AC:

AN:

60396

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

AlphaMissense

Benign

0.083

BayesDel_addAF

Benign

-0.21

BayesDel_noAF

Benign

-0.54

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.083

Eigen

Uncertain

0.26

Eigen_PC

Benign

0.21

FATHMM_MKL

Benign

0.33

LIST_S2

Benign

0.85

M_CAP

Benign

0.0073

MetaRNN

Benign

0.18

MetaSVM

Benign

-0.86

PhyloP100

0.88

PrimateAI

Uncertain

0.50

PROVEAN

Benign

-0.80

REVEL

Benign

0.078

Sift

Benign

0.081

Sift4G

Benign

0.26

Polyphen

0.92

Vest4

0.40

MutPred

0.32

Loss of disorder (P = 0.1405)

MVP

0.18

MPC

0.24

ClinPred

0.89

GERP RS

4.4

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.091

gMVP

0.12

Mutation Taster

=93/7

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

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