rs41310885

chr1-151002495-T-Achr1-151002495-T-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001376665.1(MINDY1):c.123A>T(p.Arg41Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0643 in 1,614,132 control chromosomes in the GnomAD database, including 3,848 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/19 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.077 (550 hom., cov: 32)
  • Exomes 𝑓: 0.063 (3298 hom.)
• Consequence: MINDY1 NM_001376665.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.215

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0016584694).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.127 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MINDY1	NM_001376665.1	c.123A>T	p.Arg41Ser	missense_variant	2/10	ENST00000683666.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MINDY1	ENST00000683666.2	c.123A>T	p.Arg41Ser	missense_variant	2/10		NM_001376665.1	P1

Frequencies

GnomAD3 genomes AF: 0.0767 AC: 11668 AN: 152122 Hom.: 548 Cov.: 32

Gnomad AFR AF: 0.130

Gnomad AMI AF: 0.0352

Gnomad AMR AF: 0.0430

Gnomad ASJ AF: 0.0551

Gnomad EAS AF: 0.000192

Gnomad SAS AF: 0.0106

Gnomad FIN AF: 0.0719

Gnomad MID AF: 0.0443

Gnomad NFE AF: 0.0653

Gnomad OTH AF: 0.0660

GnomAD3 exomes AF: 0.0515 AC: 12956 AN: 251462 Hom.: 434 AF XY: 0.0487 AC XY: 6622 AN XY: 135908

Gnomad AFR exome AF: 0.135

Gnomad AMR exome AF: 0.0233

Gnomad ASJ exome AF: 0.0503

Gnomad EAS exome AF: 0.000109

Gnomad SAS exome AF: 0.0109

Gnomad FIN exome AF: 0.0689

Gnomad NFE exome AF: 0.0641

Gnomad OTH exome AF: 0.0531

GnomAD4 exome AF: 0.0630 AC: 92078 AN: 1461892 Hom.: 3298 Cov.: 31 AF XY: 0.0611 AC XY: 44453 AN XY: 727246

Gnomad4 AFR exome AF: 0.138

Gnomad4 AMR exome AF: 0.0255

Gnomad4 ASJ exome AF: 0.0524

Gnomad4 EAS exome AF: 0.0000756

Gnomad4 SAS exome AF: 0.0125

Gnomad4 FIN exome AF: 0.0644

Gnomad4 NFE exome AF: 0.0687

Gnomad4 OTH exome AF: 0.0636

GnomAD4 genome AF: 0.0767 AC: 11674 AN: 152240 Hom.: 550 Cov.: 32 AF XY: 0.0744 AC XY: 5540 AN XY: 74460

Gnomad4 AFR AF: 0.130

Gnomad4 AMR AF: 0.0429

Gnomad4 ASJ AF: 0.0551

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.0108

Gnomad4 FIN AF: 0.0719

Gnomad4 NFE AF: 0.0653

Gnomad4 OTH AF: 0.0653

Alfa AF: 0.0651 Hom.: 275

Bravo AF: 0.0767

TwinsUK AF: 0.0663 AC: 246

ALSPAC AF: 0.0690 AC: 266

ESP6500AA AF: 0.133 AC: 584

ESP6500EA AF: 0.0714 AC: 614

ExAC AF: 0.0534 AC: 6482

Asia WGS AF: 0.0130 AC: 44 AN: 3478

EpiCase AF: 0.0626

EpiControl AF: 0.0583

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.10
BayesDel_addAF	Benign	-0.72	T
BayesDel_noAF	Benign	-0.71
Cadd	Benign	2.2
Dann	Benign	0.89
DEOGEN2	Benign	0.0021	T;T;.
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.067	N
LIST_S2	Benign	0.71	T;.;T
MetaRNN	Benign	0.0017	T;T;T
MetaSVM	Benign	-1.1	T
MutationTaster	Benign	1.0	P;P;P;P
PrimateAI	Benign	0.28	T
Sift4G	Benign	0.82	T;T;T
Polyphen		0.013	B;B;B
Vest4		0.035
MutPred		0.14		Gain of phosphorylation at R41 (P = 0.0101);Gain of phosphorylation at R41 (P = 0.0101);.;
MPC		0.29
ClinPred		0.0044	T
GERP RS		-0.099
Varity_R		0.079
gMVP		0.094

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

LitVar

Other links and lift over

dbSNP: rs41310885; hg19: chr1-150974971; COSMIC: COSV56498781; COSMIC: COSV56498781;