1-150997330-C-G

Variant names:

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

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_001376665.1(MINDY1):​c.1367G>C​(p.Arg456Pro) variant causes a missense change. The variant allele was found at a frequency of 0.00000276 in 1,449,682 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R456H) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000028 (0 hom.)
• Consequence: MINDY1 NM_001376665.1 missense
• Clinical Significance: Not reported in ClinVar
• 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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

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>C	p.Arg456Pro	missense	Exon 10 of 10	NP_001363594.1	Q8N5J2-1
	MINDY1	NM_001376664.1		c.1370G>C	p.Arg457Pro	missense	Exon 10 of 10	NP_001363593.1
	MINDY1	NM_001163258.3		c.1367G>C	p.Arg456Pro	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>C	p.Arg456Pro	missense	Exon 10 of 10	ENSP00000507359.1	Q8N5J2-1
	MINDY1	ENST00000361936.9	TSL:1	c.1367G>C	p.Arg456Pro	missense	Exon 11 of 11	ENSP00000354814.5	Q8N5J2-1
	MINDY1	ENST00000943009.1		c.1379G>C	p.Arg460Pro	missense	Exon 10 of 10	ENSP00000613068.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000276 AC: 4 AN: 1449682 Hom.: 0 Cov.: 31 AF XY: 0.00000417 AC XY: 3 AN XY: 720096

African (AFR) AF: 0.00 AC: 0 AN: 33136

American (AMR) AF: 0.00 AC: 0 AN: 43964

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25812

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

South Asian (SAS) AF: 0.0000356 AC: 3 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: 0.00 AC: 0 AN: 1105200

Other (OTH) AF: 0.0000167 AC: 1 AN: 59800

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.19
BayesDel_addAF	Uncertain	0.056	T
BayesDel_noAF	Benign	-0.16
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Benign	0.0027	T
Eigen	Uncertain	0.40
Eigen_PC	Uncertain	0.35
FATHMM_MKL	Uncertain	0.89	D
LIST_S2	Benign	0.84	T
M_CAP	Benign	0.025	D
MetaRNN	Uncertain	0.44	T
MetaSVM	Benign	-0.93	T
PhyloP100		4.2
PrimateAI	Benign	0.43	T
PROVEAN	Benign	0.17	N
REVEL	Benign	0.21
Sift	Uncertain	0.016	D
Sift4G	Uncertain	0.013	D
Polyphen		0.99	D
Vest4		0.39
MutPred		0.40		Loss of MoRF binding (P = 0.0067)
MVP		0.72
MPC		1.0
ClinPred		0.79	D
GERP RS		4.9
Varity_R		0.41
gMVP		0.44
Mutation Taster		=52/48	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.090		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;