rs373831013

Variant names:

• chr1-150997652-C-T
• rs373831013
• NM_001376665.1:c.1301G>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001376665.1(MINDY1):​c.1301G>A​(p.Arg434Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000143 in 1,611,430 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict 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. R434W) has been classified as Likely benign.

• Frequency:
  • Genomes: 𝑓 0.000020 (0 hom., cov: 33)
  • Exomes 𝑓: 0.000014 (0 hom.)
• Consequence: MINDY1 NM_001376665.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.637
• Publications: 2 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.038912565).

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.1301G>A	p.Arg434Gln	missense	Exon 9 of 10	NP_001363594.1	Q8N5J2-1
	MINDY1	NM_001376664.1		c.1304G>A	p.Arg435Gln	missense	Exon 9 of 10	NP_001363593.1
	MINDY1	NM_001163258.3		c.1301G>A	p.Arg434Gln	missense	Exon 10 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.1301G>A	p.Arg434Gln	missense	Exon 9 of 10	ENSP00000507359.1	Q8N5J2-1
	MINDY1	ENST00000361936.9	TSL:1	c.1301G>A	p.Arg434Gln	missense	Exon 10 of 11	ENSP00000354814.5	Q8N5J2-1
	MINDY1	ENST00000943009.1		c.1313G>A	p.Arg438Gln	missense	Exon 9 of 10	ENSP00000613068.1

Frequencies

GnomAD3 genomes AF: 0.0000197 AC: 3 AN: 152258 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.0000723

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: 0.00

GnomAD2 exomes AF: 0.0000161 AC: 4 AN: 248366 AF XY: 0.0000223

Gnomad AFR exome AF: 0.000124

Gnomad AMR exome AF: 0.0000290

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000544

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000137 AC: 20 AN: 1459172 Hom.: 0 Cov.: 34 AF XY: 0.0000193 AC XY: 14 AN XY: 725978

African (AFR) AF: 0.000149 AC: 5 AN: 33480

American (AMR) AF: 0.0000224 AC: 1 AN: 44712

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26132

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39700

South Asian (SAS) AF: 0.0000348 AC: 3 AN: 86248

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 50764

Middle Eastern (MID) AF: 0.000173 AC: 1 AN: 5768

European-Non Finnish (NFE) AF: 0.00000629 AC: 7 AN: 1111998

Other (OTH) AF: 0.0000331 AC: 2 AN: 60370

GnomAD4 genome AF: 0.0000197 AC: 3 AN: 152258 Hom.: 0 Cov.: 33 AF XY: 0.0000269 AC XY: 2 AN XY: 74390

African (AFR) AF: 0.0000723 AC: 3 AN: 41478

American (AMR) AF: 0.00 AC: 0 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5192

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

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10626

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

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

Other (OTH) AF: 0.00 AC: 0 AN: 2094

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000264

ESP6500AA AF: 0.000227 AC: 1

ESP6500EA AF: 0.00 AC: 0

ExAC AF: 0.0000247 AC: 3

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	0.058
BayesDel_addAF	Benign	-0.49	T
BayesDel_noAF	Benign	-0.70
CADD	Benign	1.3
DANN	Benign	0.58
DEOGEN2	Benign	0.00029	T
Eigen	Benign	-1.7
Eigen_PC	Benign	-1.6
FATHMM_MKL	Benign	0.024	N
LIST_S2	Benign	0.45	T
M_CAP	Benign	0.0013	T
MetaRNN	Benign	0.039	T
MetaSVM	Benign	-1.0	T
PhyloP100		-0.64
PrimateAI	Benign	0.32	T
PROVEAN	Benign	0.73	N
REVEL	Benign	0.024
Sift	Benign	1.0	T
Sift4G	Benign	0.70	T
Polyphen		0.0020	B
Vest4		0.11
MVP		0.13
MPC		0.28
ClinPred		0.014	T
GERP RS		-2.3
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.015
gMVP		0.21
Mutation Taster		=96/4	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: rs373831013; hg19: chr1-150970128;