1-150997694-T-C

Variant names:

• chr1-150997694-T-C
• rs1358304933
• NM_001376665.1:c.1259A>G

Variant summary

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

The NM_001376665.1(MINDY1):​c.1259A>G​(p.Gln420Arg) variant causes a missense change. The variant allele was found at a frequency of 0.00000274 in 1,461,338 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000027 (0 hom.)
• Consequence: MINDY1 NM_001376665.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.44

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 Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MINDY1	NM_001376665.1	c.1259A>G	p.Gln420Arg	missense_variant	Exon 9 of 10	ENST00000683666.2	NP_001363594.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MINDY1	ENST00000683666.2	c.1259A>G	p.Gln420Arg	missense_variant	Exon 9 of 10		NM_001376665.1	ENSP00000507359.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000274 AC: 4 AN: 1461338 Hom.: 0 Cov.: 34 AF XY: 0.00000275 AC XY: 2 AN XY: 726990

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000360

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

Bravo AF: 0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Jul 23, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.1403A>G (p.Q468R) alteration is located in exon 10 (coding exon 9) of the FAM63A gene. This alteration results from a A to G substitution at nucleotide position 1403, causing the glutamine (Q) at amino acid position 468 to be replaced by an arginine (R). 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	0.36
BayesDel_addAF	Pathogenic	0.17	D
BayesDel_noAF	Uncertain	0.010
CADD	Pathogenic	26
DANN	Uncertain	1.0
DEOGEN2	Benign	0.16	T;.;T;.;.
Eigen	Uncertain	0.39
Eigen_PC	Uncertain	0.38
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.88	D;D;.;D;D
M_CAP	Benign	0.053	D
MetaRNN	Uncertain	0.56	D;D;D;D;D
MetaSVM	Benign	-0.36	T
PrimateAI	Uncertain	0.56	T
PROVEAN	Uncertain	-2.4	.;N;N;N;N
REVEL	Uncertain	0.30
Sift	Uncertain	0.0030	.;D;T;D;D
Sift4G	Benign	0.17	T;T;T;T;T
Polyphen		0.99	D;.;D;D;.
Vest4		0.62
MutPred		0.31		Gain of MoRF binding (P = 0.1577);.;Gain of MoRF binding (P = 0.1577);.;.;
MVP		0.63
MPC		0.90
ClinPred		0.98	D
GERP RS		4.5
Varity_R		0.49
gMVP		0.81

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

LitVar

Other links and lift over

dbSNP: rs1358304933; hg19: chr1-150970170;