7-30791187-T-C

Position:

chr7-30791187-T-C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_032222.3(MINDY4):c.686T>C(p.Leu229Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000291 in 1,613,466 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000026 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000029 ( 0 hom. )

Consequence

MINDY4
NM_032222.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.14

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:

INMT-MINDY4 (HGNC:):

INMT-MINDY4 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.09479904).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MINDY4	NM_032222.3 linkuse as main transcript	c.686T>C	p.Leu229Pro	missense_variant	5/18	ENST00000265299.6	NP_115598.2
INMT-MINDY4	NR_037598.1 linkuse as main transcript	n.1215T>C		non_coding_transcript_exon_variant	7/20

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
MINDY4	ENST00000265299.6 linkuse as main transcript	c.686T>C	p.Leu229Pro	missense_variant	5/18	1	NM_032222.3	ENSP00000265299.6	Q4G0A6
INMT-MINDY4	ENST00000458257.5 linkuse as main transcript	n.*773T>C		non_coding_transcript_exon_variant	7/20	2		ENSP00000456039.1	F8WBC2
INMT-MINDY4	ENST00000458257.5 linkuse as main transcript	n.*773T>C		3_prime_UTR_variant	7/20	2		ENSP00000456039.1	F8WBC2
INMT-MINDY4	ENST00000451002.2 linkuse as main transcript	n.*616T>C		downstream_gene_variant		5		ENSP00000456833.2	H3BSR8

Frequencies

GnomAD3 genomes

AF:

0.0000263

AC:

AN:

152142

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000441

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.00000402

AC:

AN:

249036

Hom.:

AF XY:

0.00000740

AC XY:

AN XY:

135124

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000290

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000294

AC:

AN:

1461324

Hom.:

Cov.:

AF XY:

0.0000248

AC XY:

AN XY:

726880

show subpopulations

Gnomad4 AFR exome

AF:

0.0000598

Gnomad4 AMR exome

AF:

0.0000224

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:

0.0000351

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

AF:

0.0000263

AC:

AN:

152142

Hom.:

Cov.:

AF XY:

0.0000404

AC XY:

AN XY:

74320

show subpopulations

Gnomad4 AFR

AF:

0.0000241

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000441

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000450

Hom.:

Bravo

AF:

0.0000227

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 08, 2022

The c.686T>C (p.L229P) alteration is located in exon 5 (coding exon 5) of the FAM188B gene. This alteration results from a T to C substitution at nucleotide position 686, causing the leucine (L) at amino acid position 229 to be replaced by a proline (P). 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

0.079

BayesDel_addAF

Benign

-0.14

BayesDel_noAF

Benign

-0.36

CADD

Benign

DANN

Benign

0.89

DEOGEN2

Benign

0.0070

Eigen

Benign

-0.19

Eigen_PC

Benign

-0.13

FATHMM_MKL

Benign

0.74

LIST_S2

Benign

0.34

M_CAP

Benign

0.014

MetaRNN

Benign

0.095

MetaSVM

Benign

-1.0

PrimateAI

Benign

0.40

PROVEAN

Benign

-1.5

REVEL

Benign

0.18

Sift

Benign

0.26

Sift4G

Benign

0.34

Polyphen

0.14

Vest4

0.26

MutPred

0.16

Gain of glycosylation at L229 (P = 0.0141);

MVP

0.30

MPC

0.073

ClinPred

0.18

GERP RS

4.2

Varity_R

0.34

gMVP

0.37

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