1-151001302-A-G

Position:

• chr1-151001302-A-G

Variant summary

Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2 PP3_Strong

The NM_001376665.1(MINDY1):​c.524T>C​(p.Leu175Pro) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: MINDY1 NM_001376665.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 8.99

Genes affected

MINDY1 (HGNC:25648): (MINDY lysine 48 deubiquitinase 1) Enables K48-linked polyubiquitin modification-dependent protein binding activity; Lys48-specific deubiquitinase activity; and cysteine-type carboxypeptidase activity. Predicted to be involved in protein K48-linked deubiquitination. Located in nuclear body. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Likely_pathogenic. Variant got 6 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.952

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MINDY1	NM_001376665.1	c.524T>C	p.Leu175Pro	missense_variant	4/10	ENST00000683666.2	NP_001363594.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MINDY1	ENST00000683666.2	c.524T>C	p.Leu175Pro	missense_variant	4/10		NM_001376665.1	ENSP00000507359	P1

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 20, 2024

The c.668T>C (p.L223P) alteration is located in exon 5 (coding exon 4) of the FAM63A gene. This alteration results from a T to C substitution at nucleotide position 668, causing the leucine (L) at amino acid position 223 to be replaced by a proline (P). 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	Pathogenic	0.89
BayesDel_addAF	Pathogenic	0.32	D
BayesDel_noAF	Pathogenic	0.22
CADD	Pathogenic	27
DANN	Uncertain	1.0
DEOGEN2	Benign	0.31	T;.;T;.;.
Eigen	Uncertain	0.66
Eigen_PC	Uncertain	0.63
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Benign	0.84	T;T;.;T;T
M_CAP	Benign	0.067	D
MetaRNN	Pathogenic	0.95	D;D;D;D;D
MetaSVM	Benign	-0.39	T
MutationTaster	Benign	1.0	D;D;D;D
PrimateAI	Uncertain	0.68	T
PROVEAN	Pathogenic	-5.6	.;D;D;D;D
REVEL	Pathogenic	0.72
Sift	Uncertain	0.026	.;D;D;D;D
Sift4G	Uncertain	0.023	D;D;D;D;D
Polyphen		0.57	P;.;P;P;.
Vest4		0.97
MutPred		0.80		Gain of disorder (P = 0.0166);.;Gain of disorder (P = 0.0166);.;.;
MVP		0.83
MPC		1.0
ClinPred		0.99	D
GERP RS		5.4
Varity_R		0.96
gMVP		0.95

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: chr1-150973778;