Variant 16-81036165-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.295C>T(p.Pro99Ser) variant causes a missense change. The variant allele was found at a frequency of 0.0000427 in 1,476,956 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00023 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000022 ( 0 hom. )

Consequence

ATMIN
NM_015251.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.32

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=0.14136496).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
ATMIN	NM_015251.3 linkuse as main transcript	c.295C>T	p.Pro99Ser	missense_variant	1/4	ENST00000299575.5	NP_056066.2
CENPN-AS1	XR_007065133.1 linkuse as main transcript	n.87-1239G>A		intron_variant, non_coding_transcript_variant
CENPN-AS1	XR_007065134.1 linkuse as main transcript	n.3575+572G>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.295C>T	p.Pro99Ser	missense_variant	1/4	1	NM_015251.3	ENSP00000299575	P1	O43313-1
ATMIN	ENST00000562969.1 linkuse as main transcript	n.108C>T		non_coding_transcript_exon_variant	1/2	2

Frequencies

GnomAD3 genomes

AF:

0.000227

AC:

AN:

149710

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000776

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000133

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000699

AC:

AN:

171552

Hom.:

AF XY:

0.0000715

AC XY:

AN XY:

97964

show subpopulations

Gnomad AFR exome

AF:

0.00110

Gnomad AMR exome

AF:

0.0000409

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:

0.0000251

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000219

AC:

AN:

1327138

Hom.:

Cov.:

AF XY:

0.0000242

AC XY:

AN XY:

661516

show subpopulations

Gnomad4 AFR exome

AF:

0.000811

Gnomad4 AMR exome

AF:

0.0000298

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:

0.00000480

Gnomad4 OTH exome

AF:

0.0000191

GnomAD4 genome

AF:

0.000227

AC:

AN:

149818

Hom.:

Cov.:

AF XY:

0.000260

AC XY:

AN XY:

73122

show subpopulations

Gnomad4 AFR

AF:

0.000774

Gnomad4 AMR

AF:

0.000133

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000233

Hom.:

Bravo

AF:

0.000283

ESP6500AA

AF:

0.000244

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.0000850

AC:

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

Mar 06, 2023

The c.295C>T (p.P99S) 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 295, causing the proline (P) at amino acid position 99 to be replaced by a serine (S). 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

0.95

BayesDel_addAF

Benign

-0.42

BayesDel_noAF

Benign

-0.43

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Benign

0.065

Eigen

Uncertain

0.46

Eigen_PC

Uncertain

0.44

FATHMM_MKL

Benign

0.65

LIST_S2

Benign

0.82

M_CAP

Pathogenic

0.74

MetaRNN

Benign

0.14

MetaSVM

Benign

-0.99

MutationAssessor

Uncertain

2.2

MutationTaster

Benign

1.0

PrimateAI

Pathogenic

0.83

PROVEAN

Benign

-1.6

REVEL

Benign

0.13

Sift

Benign

0.076

Sift4G

Pathogenic

0.0

Polyphen

0.99

Vest4

0.49

MVP

0.45

MPC

0.076

ClinPred

0.12

GERP RS

4.2

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.6

Varity_R

0.29

gMVP

0.55

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