NM_001376665.1:c.1367G>T

Variant names:

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

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>T​(p.Arg456Leu) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 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)
• 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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.3779462).

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>T	p.Arg456Leu	missense	Exon 10 of 10	NP_001363594.1	Q8N5J2-1
	MINDY1	NM_001376664.1		c.1370G>T	p.Arg457Leu	missense	Exon 10 of 10	NP_001363593.1
	MINDY1	NM_001163258.3		c.1367G>T	p.Arg456Leu	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>T	p.Arg456Leu	missense	Exon 10 of 10	ENSP00000507359.1	Q8N5J2-1
	MINDY1	ENST00000361936.9	TSL:1	c.1367G>T	p.Arg456Leu	missense	Exon 11 of 11	ENSP00000354814.5	Q8N5J2-1
	MINDY1	ENST00000943009.1		c.1379G>T	p.Arg460Leu	missense	Exon 10 of 10	ENSP00000613068.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD2 exomes AF: 0.00000436 AC: 1 AN: 229512 AF XY: 0.00000804

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000996

Gnomad OTH exome AF: 0.00

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

ExAC AF: 0.00000824 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.22
BayesDel_addAF	Uncertain	0.049	T
BayesDel_noAF	Benign	-0.17
CADD	Benign	22
DANN	Uncertain	1.0
DEOGEN2	Benign	0.025	T
Eigen	Uncertain	0.31
Eigen_PC	Uncertain	0.29
FATHMM_MKL	Uncertain	0.89	D
LIST_S2	Uncertain	0.86	D
M_CAP	Benign	0.033	D
MetaRNN	Benign	0.38	T
MetaSVM	Benign	-0.95	T
PhyloP100		4.2
PrimateAI	Benign	0.42	T
PROVEAN	Uncertain	-2.4	N
REVEL	Benign	0.18
Sift	Uncertain	0.020	D
Sift4G	Uncertain	0.016	D
Polyphen		0.91	P
Vest4		0.38
MutPred		0.45		Gain of ubiquitination at K461 (P = 0.0416)
MVP		0.69
MPC		0.75
ClinPred		0.78	D
GERP RS		4.9
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.32
gMVP		0.39
Mutation Taster		=50/50

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		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;