NM_001040450.3:c.475A>G

Variant names:

• chr15-58771870-A-G
• rs1900437526
• NM_001040450.3:c.475A>G

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001040450.3(MINDY2):​c.475A>G​(p.Ser159Gly) 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. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: MINDY2 NM_001040450.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.42
• Publications: 0 publications found

Genes affected

MINDY2 (HGNC:26954): (MINDY lysine 48 deubiquitinase 2) Enables cysteine-type peptidase activity and polyubiquitin modification-dependent protein binding activity. Predicted to be involved in protein K48-linked deubiquitination. Located in nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

MINDY2-DT (HGNC:55889): (MINDY2 divergent transcript)

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.109493464).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001040450.3. 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
	MINDY2	NM_001040450.3	MANE Select	c.475A>G	p.Ser159Gly	missense	Exon 1 of 9	NP_001035540.1	Q8NBR6-1
	MINDY2	NM_001040453.3		c.475A>G	p.Ser159Gly	missense	Exon 1 of 9	NP_001035543.1	Q8NBR6-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MINDY2	ENST00000559228.6	TSL:2 MANE Select	c.475A>G	p.Ser159Gly	missense	Exon 1 of 9	ENSP00000452885.1	Q8NBR6-1
	MINDY2	ENST00000450403.3	TSL:1	c.475A>G	p.Ser159Gly	missense	Exon 1 of 9	ENSP00000393231.2	Q8NBR6-2
	MINDY2	ENST00000316848.9	TSL:1	n.475A>G		non_coding_transcript_exon	Exon 1 of 8	ENSP00000326194.5	J3KNL7

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

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	0.076
BayesDel_addAF	Benign	-0.11	T
BayesDel_noAF	Benign	-0.39
CADD	Benign	20
DANN	Uncertain	0.99
DEOGEN2	Benign	0.018	T
Eigen	Benign	-0.30
Eigen_PC	Benign	-0.14
FATHMM_MKL	Benign	0.37	N
LIST_S2	Benign	0.68	T
M_CAP	Benign	0.028	D
MetaRNN	Benign	0.11	T
MetaSVM	Benign	-1.1	T
PhyloP100		2.4
PrimateAI	Uncertain	0.73	T
PROVEAN	Benign	-0.020	N
REVEL	Benign	0.083
Sift	Benign	0.11	T
Sift4G	Benign	0.51	T
Polyphen		0.0010	B
Vest4		0.27
MutPred		0.18		Loss of phosphorylation at S159 (P = 0.0042)
MVP		0.37
MPC		0.21
ClinPred		0.81	D
GERP RS		4.0
Varity_R		0.18
gMVP		0.11

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: rs1900437526; hg19: chr15-59064069;