7-30781983-G-C

Position:

• chr7-30781983-G-C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_032222.3(MINDY4):​c.190G>C​(p.Glu64Gln) variant causes a missense 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. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: MINDY4 NM_032222.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.86

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]

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]

MINDY4 (HGNC:):

ACMG classification

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=0.21787494).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MINDY4	NM_032222.3	c.190G>C	p.Glu64Gln	missense_variant	3/18	ENST00000265299.6	NP_115598.2
INMT-MINDY4	NR_037598.1	n.719G>C		non_coding_transcript_exon_variant	5/20

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MINDY4	ENST00000265299.6	c.190G>C	p.Glu64Gln	missense_variant	3/18	1	NM_032222.3	ENSP00000265299.6
INMT-MINDY4	ENST00000458257.5	n.*277G>C		non_coding_transcript_exon_variant	5/20	2		ENSP00000456039.1
INMT-MINDY4	ENST00000458257.5	n.*277G>C		3_prime_UTR_variant	5/20	2		ENSP00000456039.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD3 exomes AF: 0.00000403 AC: 1 AN: 248172 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 134574

Gnomad AFR exome AF: 0.0000647

Gnomad AMR exome AF: 0.00

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 Cov.: 31

GnomAD4 genome Cov.: 33

Bravo AF: 0.00000378

ExAC AF: 0.00000828 AC: 1

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

May 17, 2023

The c.190G>C (p.E64Q) alteration is located in exon 3 (coding exon 3) of the FAM188B gene. This alteration results from a G to C substitution at nucleotide position 190, causing the glutamic acid (E) at amino acid position 64 to be replaced by a glutamine (Q). 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	0.12
BayesDel_addAF	Benign	-0.29	T
BayesDel_noAF	Benign	-0.47
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.083	T
Eigen	Uncertain	0.53
Eigen_PC	Uncertain	0.53
FATHMM_MKL	Uncertain	0.87	D
LIST_S2	Uncertain	0.87	D
M_CAP	Benign	0.0059	T
MetaRNN	Benign	0.22	T
MetaSVM	Benign	-1.0	T
PrimateAI	Benign	0.39	T
PROVEAN	Benign	-1.3	N
REVEL	Benign	0.11
Sift	Uncertain	0.015	D
Sift4G	Benign	0.17	T
Polyphen		0.97	D
Vest4		0.32
MutPred		0.38		Loss of ubiquitination at K61 (P = 0.0289);
MVP		0.28
MPC		0.17
ClinPred		0.75	D
GERP RS		4.3
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.11
gMVP		0.26

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

Other links and lift over

dbSNP: rs753348251; hg19: chr7-30821599;