1-150997330-C-T

Variant names:

• chr1-150997330-C-T
• rs777714745
• NM_001376665.1:c.1367G>A

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001376665.1(MINDY1):​c.1367G>A​(p.Arg456His) variant causes a missense change. The variant allele was found at a frequency of 0.0000112 in 1,601,924 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R456C) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.0000066 (0 hom., cov: 33)
  • Exomes 𝑓: 0.000012 (0 hom.)
• Consequence: MINDY1 NM_001376665.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.22
• Publications: 0 publications found

Genes affected

MINDY1 (HGNC:25648): (MINDY lysine 48 deubiquitinase 1) Enables K48-linked polyubiquitin modification-dependent protein binding activity; Lys48-specific deubiquitinase activity; and cysteine-type carboxypeptidase activity. Predicted to be involved in protein K48-linked deubiquitination. Located in nuclear body. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.28283352).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001376665.1. 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
	MINDY1	NM_001376665.1	MANE Select	c.1367G>A	p.Arg456His	missense	Exon 10 of 10	NP_001363594.1	Q8N5J2-1
	MINDY1	NM_001376664.1		c.1370G>A	p.Arg457His	missense	Exon 10 of 10	NP_001363593.1
	MINDY1	NM_001163258.3		c.1367G>A	p.Arg456His	missense	Exon 11 of 11	NP_001156730.3	Q8N5J2-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MINDY1	ENST00000683666.2	MANE Select	c.1367G>A	p.Arg456His	missense	Exon 10 of 10	ENSP00000507359.1	Q8N5J2-1
	MINDY1	ENST00000361936.9	TSL:1	c.1367G>A	p.Arg456His	missense	Exon 11 of 11	ENSP00000354814.5	Q8N5J2-1
	MINDY1	ENST00000943009.1		c.1379G>A	p.Arg460His	missense	Exon 10 of 10	ENSP00000613068.1

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152242 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.00

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: 0.00

Gnomad OTH AF: 0.000478

GnomAD2 exomes AF: 0.0000174 AC: 4 AN: 229512 AF XY: 0.0000321

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000597

Gnomad ASJ exome AF: 0.000105

Gnomad EAS 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: 0.0000117 AC: 17 AN: 1449682 Hom.: 0 Cov.: 31 AF XY: 0.0000153 AC XY: 11 AN XY: 720096

African (AFR) AF: 0.0000302 AC: 1 AN: 33136

American (AMR) AF: 0.0000682 AC: 3 AN: 43964

Ashkenazi Jewish (ASJ) AF: 0.0000387 AC: 1 AN: 25812

East Asian (EAS) AF: 0.00 AC: 0 AN: 39198

South Asian (SAS) AF: 0.0000119 AC: 1 AN: 84218

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52600

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5754

European-Non Finnish (NFE) AF: 0.00000633 AC: 7 AN: 1105200

Other (OTH) AF: 0.0000669 AC: 4 AN: 59800

GnomAD4 genome AF: 0.00000657 AC: 1 AN: 152242 Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0 AN XY: 74380

African (AFR) AF: 0.00 AC: 0 AN: 41458

American (AMR) AF: 0.00 AC: 0 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5204

South Asian (SAS) AF: 0.00 AC: 0 AN: 4836

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10630

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68040

Other (OTH) AF: 0.000478 AC: 1 AN: 2092

Alfa AF: 0.0000602 Hom.: 0

Bravo AF: 0.00000756

ExAC AF: 0.0000165 AC: 2

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.14
BayesDel_addAF	Benign	-0.13	T
BayesDel_noAF	Benign	-0.25
CADD	Uncertain	25
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.016	T
Eigen	Uncertain	0.45
Eigen_PC	Uncertain	0.39
FATHMM_MKL	Uncertain	0.88	D
LIST_S2	Uncertain	0.89	D
M_CAP	Benign	0.038	D
MetaRNN	Benign	0.28	T
MetaSVM	Benign	-0.84	T
PhyloP100		4.2
PrimateAI	Benign	0.42	T
PROVEAN	Benign	-1.4	N
REVEL	Benign	0.18
Sift	Benign	0.10	T
Sift4G	Uncertain	0.014	D
Polyphen		1.0	D
Vest4		0.24
MutPred		0.42		Loss of MoRF binding (P = 0.0295)
MVP		0.63
MPC		0.94
ClinPred		0.68	D
GERP RS		4.9
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.19
gMVP		0.28
Mutation Taster		=58/42	polymorphism

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

Other links and lift over

dbSNP: rs777714745; hg19: chr1-150969806;