NM_001376665.1:c.123A>C

Variant names:

• chr1-151002495-T-G
• rs41310885
• NM_001376665.1:c.123A>C

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.123A>C​(p.Arg41Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: MINDY1 NM_001376665.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.215
• Publications: 19 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=0.05275303).

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.123A>C	p.Arg41Ser	missense	Exon 2 of 10	NP_001363594.1	Q8N5J2-1
	MINDY1	NM_001376664.1		c.123A>C	p.Arg41Ser	missense	Exon 2 of 10	NP_001363593.1
	MINDY1	NM_001163258.3		c.123A>C	p.Arg41Ser	missense	Exon 3 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.123A>C	p.Arg41Ser	missense	Exon 2 of 10	ENSP00000507359.1	Q8N5J2-1
	MINDY1	ENST00000361936.9	TSL:1	c.123A>C	p.Arg41Ser	missense	Exon 3 of 11	ENSP00000354814.5	Q8N5J2-1
	MINDY1	ENST00000943009.1		c.123A>C	p.Arg41Ser	missense	Exon 2 of 10	ENSP00000613068.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ExAC AF: 0.00000824 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.10
BayesDel_addAF	Benign	-0.33	T
BayesDel_noAF	Benign	-0.71
CADD	Benign	2.3
DANN	Benign	0.89
DEOGEN2	Benign	0.0021	T
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.091	N
LIST_S2	Benign	0.71	T
M_CAP	Benign	0.0043	T
MetaRNN	Benign	0.053	T
MetaSVM	Benign	-1.1	T
PhyloP100		0.21
PrimateAI	Benign	0.28	T
PROVEAN	Benign	0.52	N
REVEL	Benign	0.032
Sift	Benign	0.17	T
Sift4G	Benign	0.82	T
Polyphen		0.013	B
Vest4		0.035
MutPred		0.14		Gain of phosphorylation at R41 (P = 0.0101)
MVP		0.16
MPC		0.29
ClinPred		0.12	T
GERP RS		-0.099
Varity_R		0.079
gMVP		0.094
Mutation Taster		=99/1	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: rs41310885; hg19: chr1-150974971;