10-15821713-T-C

Variant names:

• chr10-15821713-T-C
• NM_024948.4:c.744A>G

Variant summary

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

The NM_024948.4(MINDY3):​c.744A>G​(p.Ile248Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: MINDY3 NM_024948.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.23

Genes affected

MINDY3 (HGNC:23578): (MINDY lysine 48 deubiquitinase 3) The protein encoded by this gene contains a caspase-associated recruitment domain and may function in apoptosis. It has been identified as a tumor suppressor in lung and gastric cancers, and a polymorphism in the gene may be associated with gastric cancer risk. Alternative splicing of this gene results in multiple transcript variants. [provided by RefSeq, Dec 2015]

LOC124902383 (HGNC:):

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
MINDY3	NM_024948.4	c.744A>G	p.Ile248Met	missense_variant	Exon 9 of 15	ENST00000277632.8	NP_079224.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MINDY3	ENST00000277632.8	c.744A>G	p.Ile248Met	missense_variant	Exon 9 of 15	1	NM_024948.4	ENSP00000277632.3
MINDY3	ENST00000477891.1	n.891A>G		non_coding_transcript_exon_variant	Exon 8 of 14	1
MINDY3	ENST00000418767.5	c.264A>G	p.Ile88Met	missense_variant	Exon 4 of 7	3		ENSP00000388661.1
MINDY3	ENST00000436829.1	c.303A>G	p.Ile101Met	missense_variant	Exon 6 of 8	5		ENSP00000389883.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Sep 16, 2021

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.744A>G (p.I248M) alteration is located in exon 9 (coding exon 9) of the FAM188A gene. This alteration results from a A to G substitution at nucleotide position 744, causing the isoleucine (I) at amino acid position 248 to be replaced by a methionine (M). 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	0.58
BayesDel_addAF	Uncertain	0.12	D
BayesDel_noAF	Uncertain	-0.060
CADD	Benign	23
DANN	Uncertain	0.99
DEOGEN2	Uncertain	0.43	T;.;T
Eigen	Uncertain	0.47
Eigen_PC	Uncertain	0.37
FATHMM_MKL	Uncertain	0.81	D
LIST_S2	Uncertain	0.93	D;D;D
M_CAP	Benign	0.049	D
MetaRNN	Uncertain	0.68	D;D;D
MetaSVM	Benign	-0.69	T
PrimateAI	Uncertain	0.77	T
PROVEAN	Uncertain	-2.5	N;D;D
REVEL	Uncertain	0.44
Sift	Uncertain	0.0040	D;D;D
Sift4G	Uncertain	0.0060	D;D;.
Polyphen		1.0	D;.;.
Vest4		0.80
MutPred		0.69		Gain of disorder (P = 0.0608);.;.;
MVP		0.33
MPC		0.60
ClinPred		0.99	D
GERP RS		2.8
Varity_R		0.52
gMVP		0.76

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: chr10-15863712;