7-30781983-G-A

Position:

• chr7-30781983-G-A

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>A​(p.Glu64Lys) 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. 13/20 in silico tools predict 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=0.122385114).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MINDY4	NM_032222.3	c.190G>A	p.Glu64Lys	missense_variant	3/18	ENST00000265299.6	NP_115598.2
INMT-MINDY4	NR_037598.1	n.719G>A		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>A	p.Glu64Lys	missense_variant	3/18	1	NM_032222.3	ENSP00000265299.6
INMT-MINDY4	ENST00000458257.5	n.*277G>A		non_coding_transcript_exon_variant	5/20	2		ENSP00000456039.1
INMT-MINDY4	ENST00000458257.5	n.*277G>A		3_prime_UTR_variant	5/20	2		ENSP00000456039.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

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

Jan 31, 2024

The c.190G>A (p.E64K) alteration is located in exon 3 (coding exon 3) of the FAM188B gene. This alteration results from a G to A substitution at nucleotide position 190, causing the glutamic acid (E) at amino acid position 64 to be replaced by a lysine (K). 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	0.10
BayesDel_addAF	Benign	-0.16	T
BayesDel_noAF	Benign	-0.47
CADD	Benign	22
DANN	Uncertain	1.0
DEOGEN2	Benign	0.0061	T
Eigen	Benign	0.14
Eigen_PC	Uncertain	0.25
FATHMM_MKL	Uncertain	0.80	D
LIST_S2	Benign	0.82	T
M_CAP	Benign	0.0057	T
MetaRNN	Benign	0.12	T
MetaSVM	Benign	-1.0	T
PrimateAI	Benign	0.46	T
PROVEAN	Benign	-1.5	N
REVEL	Benign	0.099
Sift	Benign	0.099	T
Sift4G	Benign	0.36	T
Polyphen		0.071	B
Vest4		0.24
MutPred		0.49		Gain of methylation at E64 (P = 0.0074);
MVP		0.14
MPC		0.054
ClinPred		0.75	D
GERP RS		4.3
Varity_R		0.12
gMVP		0.27

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr7-30821599;