Variant 15-79456772-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3

The NM_015206.3(MINAR1):c.625T>C(p.Cys209Arg) variant causes a missense change. The variant allele was found at a frequency of 0.00007 in 1,614,202 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000046 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000073 ( 0 hom. )

Consequence

MINAR1
NM_015206.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.56

Variant links:

Genes affected

MINAR1 (HGNC:29172): (membrane integral NOTCH2 associated receptor 1) Involved in several processes, including negative regulation of TOR signaling; negative regulation of angiogenesis; and negative regulation of protein ubiquitination. Located in plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

MINAR1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.819

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MINAR1	NM_015206.3 linkuse as main transcript	c.625T>C	p.Cys209Arg	missense_variant	2/4	ENST00000305428.8	NP_056021.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MINAR1	ENST00000305428.8 linkuse as main transcript	c.625T>C	p.Cys209Arg	missense_variant	2/4	1	NM_015206.3	ENSP00000307461	P1
MINAR1	ENST00000559272.1 linkuse as main transcript	c.625T>C	p.Cys209Arg	missense_variant, NMD_transcript_variant	1/4	1		ENSP00000454088

Frequencies

GnomAD3 genomes

AF:

0.0000460

AC:

AN:

152190

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000103

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000517

AC:

AN:

251474

Hom.:

AF XY:

0.0000662

AC XY:

AN XY:

135912

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000578

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000967

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000725

AC:

106

AN:

1461894

Hom.:

Cov.:

AF XY:

0.0000756

AC XY:

AN XY:

727248

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000447

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:

0.0000917

Gnomad4 OTH exome

AF:

0.0000331

GnomAD4 genome

AF:

0.0000460

AC:

AN:

152308

Hom.:

Cov.:

AF XY:

0.0000268

AC XY:

AN XY:

74488

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000103

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000594

Hom.:

Bravo

AF:

0.0000378

ExAC

AF:

0.0000494

AC:

EpiCase

AF:

0.0000545

EpiControl

AF:

0.00

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Oct 05, 2022

The c.625T>C (p.C209R) alteration is located in exon 2 (coding exon 1) of the KIAA1024 gene. This alteration results from a T to C substitution at nucleotide position 625, causing the cysteine (C) at amino acid position 209 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

Pathogenic

0.58

BayesDel_addAF

Uncertain

0.080

BayesDel_noAF

Uncertain

0.090

CADD

Uncertain

DANN

Uncertain

1.0

Eigen

Uncertain

0.62

Eigen_PC

Uncertain

0.61

FATHMM_MKL

Uncertain

0.93

LIST_S2

Benign

0.69

M_CAP

Uncertain

0.12

MetaRNN

Pathogenic

0.82

MetaSVM

Benign

-0.77

MutationTaster

Benign

1.0

PrimateAI

Pathogenic

0.79

PROVEAN

Pathogenic

-10

REVEL

Uncertain

0.31

Sift

Benign

0.043

Sift4G

Benign

0.17

Vest4

0.90

MVP

0.21

MPC

0.51

ClinPred

0.65

GERP RS

5.5

gMVP

0.56

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over