15-58771870-A-G

Position:

• chr15-58771870-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.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. 13/20 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

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=0.109493464).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MINDY2	NM_001040450.3	c.475A>G	p.Ser159Gly	missense_variant	1/9	ENST00000559228.6	NP_001035540.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MINDY2	ENST00000559228.6	c.475A>G	p.Ser159Gly	missense_variant	1/9	2	NM_001040450.3	ENSP00000452885	P2
MINDY2	ENST00000450403.3	c.475A>G	p.Ser159Gly	missense_variant	1/9	1		ENSP00000393231	A2
MINDY2	ENST00000316848.9	c.475A>G	p.Ser159Gly	missense_variant, NMD_transcript_variant	1/8	1		ENSP00000326194
MINDY2	ENST00000560289.5	c.475A>G	p.Ser159Gly	missense_variant, NMD_transcript_variant	1/9	1		ENSP00000453425

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

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

May 23, 2023

The c.475A>G (p.S159G) alteration is located in exon 1 (coding exon 1) of the FAM63B gene. This alteration results from a A to G substitution at nucleotide position 475, causing the serine (S) at amino acid position 159 to be replaced by a glycine (G). 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	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;T
M_CAP	Benign	0.028	D
MetaRNN	Benign	0.11	T;T
MetaSVM	Benign	-1.1	T
MutationTaster	Benign	0.81	N;N
PrimateAI	Uncertain	0.73	T
PROVEAN	Benign	-0.020	N;N
REVEL	Benign	0.083
Sift	Benign	0.11	T;T
Sift4G	Benign	0.51	T;T
Polyphen		0.0010	B;B
Vest4		0.27
MutPred		0.18		Loss of phosphorylation at S159 (P = 0.0042);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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr15-59064069;