15-58787930-A-G

Position:

• chr15-58787930-A-G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001040450.3(MINDY2):​c.865A>G​(p.Ile289Val) 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. 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: 5.44

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.15932524).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MINDY2	NM_001040450.3	c.865A>G	p.Ile289Val	missense_variant	2/9	ENST00000559228.6	NP_001035540.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MINDY2	ENST00000559228.6	c.865A>G	p.Ile289Val	missense_variant	2/9	2	NM_001040450.3	ENSP00000452885	P2
MINDY2	ENST00000450403.3	c.865A>G	p.Ile289Val	missense_variant	2/9	1		ENSP00000393231	A2
MINDY2	ENST00000316848.9	c.865A>G	p.Ile289Val	missense_variant, NMD_transcript_variant	2/8	1		ENSP00000326194
MINDY2	ENST00000560289.5	c.865A>G	p.Ile289Val	missense_variant, NMD_transcript_variant	2/9	1		ENSP00000453425

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 28

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Aug 20, 2023

The c.865A>G (p.I289V) alteration is located in exon 2 (coding exon 2) of the FAM63B gene. This alteration results from a A to G substitution at nucleotide position 865, causing the isoleucine (I) at amino acid position 289 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.46
BayesDel_addAF	Benign	-0.16	T
BayesDel_noAF	Benign	-0.46
CADD	Benign	21
DANN	Benign	0.94
DEOGEN2	Benign	0.0087	T;.
Eigen	Benign	-0.38
Eigen_PC	Benign	-0.093
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Uncertain	0.90	D;D
M_CAP	Benign	0.0079	T
MetaRNN	Benign	0.16	T;T
MetaSVM	Benign	-1.0	T
MutationTaster	Benign	0.98	D;D
PrimateAI	Uncertain	0.73	T
PROVEAN	Benign	-0.13	N;N
REVEL	Benign	0.18
Sift	Benign	0.43	T;T
Sift4G	Benign	0.90	T;T
Polyphen		0.083	B;B
Vest4		0.48
MutPred		0.36		Gain of catalytic residue at I289 (P = 0.0049);Gain of catalytic residue at I289 (P = 0.0049);
MVP		0.24
MPC		0.22
ClinPred		0.85	D
GERP RS		5.2
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.090
gMVP		0.25

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr15-59080129;