chr15-58771835-G-T

Position:

• chr15-58771835-G-T

Variant summary

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

The NM_001040450.3(MINDY2):​c.440G>T​(p.Gly147Val) 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: 0.688

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=0.082221776).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MINDY2	NM_001040450.3	c.440G>T	p.Gly147Val	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.440G>T	p.Gly147Val	missense_variant	1/9	2	NM_001040450.3	ENSP00000452885.1
MINDY2	ENST00000450403.3	c.440G>T	p.Gly147Val	missense_variant	1/9	1		ENSP00000393231.2
MINDY2	ENST00000316848.9	n.440G>T		non_coding_transcript_exon_variant	1/8	1		ENSP00000326194.5
MINDY2	ENST00000560289.5	n.440G>T		non_coding_transcript_exon_variant	1/9	1		ENSP00000453425.1

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

Mar 28, 2024

The c.440G>T (p.G147V) alteration is located in exon 1 (coding exon 1) of the FAM63B gene. This alteration results from a G to T substitution at nucleotide position 440, causing the glycine (G) at amino acid position 147 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	Benign	0.082
BayesDel_addAF	Benign	-0.13	T
BayesDel_noAF	Benign	-0.43
CADD	Benign	19
DANN	Benign	0.82
DEOGEN2	Benign	0.025	T;.
Eigen	Benign	-0.62
Eigen_PC	Benign	-0.59
FATHMM_MKL	Benign	0.12	N
LIST_S2	Benign	0.75	T;T
M_CAP	Benign	0.0071	T
MetaRNN	Benign	0.082	T;T
MetaSVM	Benign	-1.1	T
PrimateAI	Uncertain	0.75	T
PROVEAN	Benign	-1.1	N;N
REVEL	Benign	0.054
Sift	Benign	0.031	D;D
Sift4G	Benign	0.10	T;T
Polyphen		0.019	B;B
Vest4		0.15
MutPred		0.15		Loss of loop (P = 0.0128);Loss of loop (P = 0.0128);
MVP		0.24
MPC		0.12
ClinPred		0.081	T
GERP RS		2.3
Varity_R		0.081
gMVP		0.13

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: chr15-59064034;