Variant 16-81035917-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_015251.3(ATMIN):c.47C>T(p.Ala16Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000187 in 987,390 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00021 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00018 ( 0 hom. )

Consequence

ATMIN
NM_015251.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.0260

Variant links:

Genes affected

ATMIN (HGNC:29034): (ATM interactor) Enables dynein complex binding activity. Involved in positive regulation of transcription, DNA-templated. Located in nuclear body. [provided by Alliance of Genome Resources, Apr 2022]

ATMIN links:

CENPN-AS1 (HGNC:):

CENPN-AS1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

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=0.07366952).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
ATMIN	NM_015251.3 linkuse as main transcript	c.47C>T	p.Ala16Val	missense_variant	1/4	ENST00000299575.5	NP_056066.2
CENPN-AS1	XR_007065133.1 linkuse as main transcript	n.87-991G>A		intron_variant, non_coding_transcript_variant
CENPN-AS1	XR_007065134.1 linkuse as main transcript	n.3575+820G>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ATMIN	ENST00000299575.5 linkuse as main transcript	c.47C>T	p.Ala16Val	missense_variant	1/4	1	NM_015251.3	ENSP00000299575	P1	O43313-1

Frequencies

GnomAD3 genomes

AF:

0.000206

AC:

AN:

145936

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000737

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00233

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000243

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.000184

AC:

155

AN:

841348

Hom.:

Cov.:

AF XY:

0.000203

AC XY:

AN XY:

389464

show subpopulations

Gnomad4 AFR exome

AF:

0.0000627

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00317

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000117

Gnomad4 OTH exome

AF:

0.000324

GnomAD4 genome

AF:

0.000205

AC:

AN:

146042

Hom.:

Cov.:

AF XY:

0.000155

AC XY:

AN XY:

71058

show subpopulations

Gnomad4 AFR

AF:

0.0000735

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00233

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000243

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000214

Hom.:

Bravo

AF:

0.000140

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

Feb 22, 2023

The c.47C>T (p.A16V) alteration is located in exon 1 (coding exon 1) of the ATMIN gene. This alteration results from a C to T substitution at nucleotide position 47, causing the alanine (A) at amino acid position 16 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

0.30

BayesDel_addAF

Benign

-0.19

BayesDel_noAF

Benign

-0.51

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.058

Eigen

Benign

-0.85

Eigen_PC

Benign

-0.93

FATHMM_MKL

Benign

0.0013

LIST_S2

Benign

0.39

M_CAP

Benign

0.080

MetaRNN

Benign

0.074

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.6

MutationTaster

Benign

1.0

PrimateAI

Pathogenic

0.86

PROVEAN

Benign

-0.16

REVEL

Benign

0.038

Sift

Benign

0.072

Sift4G

Pathogenic

0.0

Polyphen

0.57

Vest4

0.33

MutPred

0.30

Gain of catalytic residue at A16 (P = 0.0649);

MVP

0.099

MPC

1.9

ClinPred

0.15

GERP RS

1.5

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

2.3

Varity_R

0.034

gMVP

0.41

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