Variant 16-81036066-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6_Moderate

The NM_015251.3(ATMIN):c.196G>A(p.Gly66Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000919 in 1,305,962 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 Likely benign (★).

Frequency

Genomes: 𝑓 0.000020 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000078 ( 0 hom. )

Consequence

ATMIN
NM_015251.3 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.0280

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 Likely_benign. Variant got -4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.029952377).

BP6

Variant 16-81036066-G-A is Benign according to our data. Variant chr16-81036066-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 2388266.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
ATMIN	NM_015251.3 linkuse as main transcript	c.196G>A	p.Gly66Arg	missense_variant	1/4	ENST00000299575.5
CENPN-AS1	XR_007065133.1 linkuse as main transcript	n.87-1140C>T		intron_variant, non_coding_transcript_variant
CENPN-AS1	XR_007065134.1 linkuse as main transcript	n.3575+671C>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ATMIN	ENST00000299575.5 linkuse as main transcript	c.196G>A	p.Gly66Arg	missense_variant	1/4	1	NM_015251.3	P1	O43313-1
ATMIN	ENST00000562969.1 linkuse as main transcript	n.9G>A		non_coding_transcript_exon_variant	1/2	2

Frequencies

GnomAD3 genomes

AF:

0.0000202

AC:

AN:

148640

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000486

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:

0.0000150

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.00000778

AC:

AN:

1157322

Hom.:

Cov.:

AF XY:

0.00000886

AC XY:

AN XY:

564138

show subpopulations

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:

0.00000947

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000202

AC:

AN:

148640

Hom.:

Cov.:

AF XY:

0.0000276

AC XY:

AN XY:

72432

show subpopulations

Gnomad4 AFR

AF:

0.0000486

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:

0.0000150

Gnomad4 OTH

AF:

0.00

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Aug 16, 2021

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.078

BayesDel_addAF

Benign

-0.28

BayesDel_noAF

Benign

-0.64

CADD

Benign

9.4

DANN

Benign

0.95

DEOGEN2

Benign

0.052

Eigen

Benign

-1.2

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.089

LIST_S2

Benign

0.49

M_CAP

Uncertain

0.10

MetaRNN

Benign

0.030

MetaSVM

Benign

-1.1

MutationAssessor

Benign

-0.17

MutationTaster

Benign

1.0

PrimateAI

Pathogenic

0.89

PROVEAN

Benign

0.38

REVEL

Benign

0.024

Sift

Benign

0.42

Sift4G

Benign

0.90

Polyphen

0.0

Vest4

0.098

MutPred

0.20

Gain of helix (P = 0.0496);

MVP

0.067

MPC

0.029

ClinPred

0.089

GERP RS

1.6

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.6

Varity_R

0.030

gMVP

0.38

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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