15-58771751-T-G

Variant names:

• chr15-58771751-T-G
• rs374853839
• NM_001040450.3:c.356T>G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001040450.3(MINDY2):​c.356T>G​(p.Val119Gly) 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. 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. V119A) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: MINDY2 NM_001040450.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0100
• Publications: 1 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: 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=0.06390536).

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.356T>G	p.Val119Gly	missense	Exon 1 of 9	NP_001035540.1	Q8NBR6-1
	MINDY2	NM_001040453.3		c.356T>G	p.Val119Gly	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.356T>G	p.Val119Gly	missense	Exon 1 of 9	ENSP00000452885.1	Q8NBR6-1
	MINDY2	ENST00000450403.3	TSL:1	c.356T>G	p.Val119Gly	missense	Exon 1 of 9	ENSP00000393231.2	Q8NBR6-2
	MINDY2	ENST00000316848.9	TSL:1	n.356T>G		non_coding_transcript_exon	Exon 1 of 8	ENSP00000326194.5	J3KNL7

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00000417 AC: 1 AN: 240086 AF XY: 0.00000758

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: 0.00000935

Gnomad OTH exome AF: 0.00

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ExAC AF: 0.00000828 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.057
BayesDel_addAF	Benign	-0.13	T
BayesDel_noAF	Benign	-0.43
CADD	Benign	16
DANN	Benign	0.91
DEOGEN2	Benign	0.025	T
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.042	N
LIST_S2	Benign	0.47	T
M_CAP	Benign	0.0057	T
MetaRNN	Benign	0.064	T
MetaSVM	Benign	-1.1	T
PhyloP100		-0.010
PrimateAI	Uncertain	0.75	T
PROVEAN	Benign	-0.66	N
REVEL	Benign	0.0060
Sift	Uncertain	0.0040	D
Sift4G	Uncertain	0.010	D
Polyphen		0.0080	B
Vest4		0.20
MutPred		0.24		Loss of sheet (P = 0.0228)
MVP		0.095
MPC		0.11
ClinPred		0.098	T
GERP RS		0.54
PromoterAI		-0.015	Neutral
Varity_R		0.089
gMVP		0.13

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: rs374853839; hg19: chr15-59063950;