Variant 16-81043163-A-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.665A>T(p.Asp222Val) variant causes a missense, splice region change. The variant allele was found at a frequency of 0.00000416 in 1,442,762 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000042 ( 0 hom. )

Consequence

ATMIN
NM_015251.3 missense, splice_region

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.65

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:

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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=0.22754666).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ATMIN	NM_015251.3 linkuse as main transcript	c.665A>T	p.Asp222Val	missense_variant, splice_region_variant	4/4	ENST00000299575.5	NP_056066.2
ATMIN	NM_001300728.2 linkuse as main transcript	c.197A>T	p.Asp66Val	missense_variant, splice_region_variant	4/4		NP_001287657.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ATMIN	ENST00000299575.5 linkuse as main transcript	c.665A>T	p.Asp222Val	missense_variant, splice_region_variant	4/4	1	NM_015251.3	ENSP00000299575	P1	O43313-1
ATMIN	ENST00000564241.5 linkuse as main transcript	c.197A>T	p.Asp66Val	missense_variant, splice_region_variant	4/4	1		ENSP00000463478		O43313-2
ATMIN	ENST00000566488.1 linkuse as main transcript	c.197A>T	p.Asp66Val	missense_variant, splice_region_variant	3/3	1		ENSP00000455497		O43313-2
ATMIN	ENST00000539819.5 linkuse as main transcript	n.423A>T		splice_region_variant, non_coding_transcript_exon_variant	3/3	2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000170

AC:

AN:

234952

Hom.:

AF XY:

0.0000157

AC XY:

AN XY:

127130

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

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:

0.0000368

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000416

AC:

AN:

1442762

Hom.:

Cov.:

AF XY:

0.00000279

AC XY:

AN XY:

717108

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:

0.00000542

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000378

ExAC

AF:

0.0000330

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

Sep 06, 2022

The c.665A>T (p.D222V) alteration is located in exon 4 (coding exon 4) of the ATMIN gene. This alteration results from a A to T substitution at nucleotide position 665, causing the aspartic acid (D) at amino acid position 222 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

0.32

BayesDel_addAF

Benign

-0.11

BayesDel_noAF

Benign

-0.28

CADD

Benign

DANN

Uncertain

0.98

DEOGEN2

Benign

0.19

T;.;.

Eigen

Benign

0.15

Eigen_PC

Uncertain

0.30

FATHMM_MKL

Uncertain

0.94

LIST_S2

Uncertain

0.88

D;.;D

M_CAP

Benign

0.012

MetaRNN

Benign

0.23

T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Uncertain

2.8

M;.;.

MutationTaster

Benign

1.0

D;D;D

PrimateAI

Uncertain

0.52

PROVEAN

Benign

-1.6

N;.;N

REVEL

Benign

0.12

Sift

Uncertain

0.022

D;.;T

Sift4G

Benign

0.076

T;T;T

Polyphen

0.14

B;.;.

Vest4

0.48

MutPred

0.21

Loss of ubiquitination at K227 (P = 0.0224);.;.;

MVP

0.30

MPC

0.053

ClinPred

0.40

GERP RS

5.9

Varity_R

0.13

gMVP

0.44

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