dbSNP rs2278022: ATMIN:p.Ser240Pro (chr16-81043216-T-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_015251.3(ATMIN):c.718T>C(p.Ser240Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0861 in 1,613,118 control chromosomes in the GnomAD database, including 6,793 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.079 ( 529 hom., cov: 32)

Exomes 𝑓: 0.087 ( 6264 hom. )

Consequence

ATMIN
NM_015251.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.27

Publications

26 publications found

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:

ENSG00000284512 (HGNC:):

ENSG00000284512 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=9.6076727E-4).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.189 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ATMIN	NM_015251.3 link	c.718T>C	p.Ser240Pro	missense_variant	Exon 4 of 4	ENST00000299575.5	NP_056066.2	O43313-1
ATMIN	NM_001300728.2 link	c.250T>C	p.Ser84Pro	missense_variant	Exon 4 of 4		NP_001287657.1	O43313-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ATMIN	ENST00000299575.5 link	c.718T>C	p.Ser240Pro	missense_variant	Exon 4 of 4	1	NM_015251.3	ENSP00000299575.3		O43313-1
ENSG00000284512	ENST00000640345.1 link	c.425-8290A>G		intron_variant	Intron 4 of 5	5		ENSP00000492798.1		A0A1W2PS29

Frequencies

GnomAD3 genomes

AF:

0.0790

AC:

12015

AN:

152038

Hom.:

528

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0454

Gnomad AMI

AF:

0.0274

Gnomad AMR

AF:

0.106

Gnomad ASJ

AF:

0.0522

Gnomad EAS

AF:

0.201

Gnomad SAS

AF:

0.0816

Gnomad FIN

AF:

0.121

Gnomad MID

AF:

0.0601

Gnomad NFE

AF:

0.0799

Gnomad OTH

AF:

0.0727

GnomAD2 exomes

AF:

0.100

AC:

25109

AN:

250652

AF XY:

0.0958

show subpopulations

Gnomad AFR exome

AF:

0.0499

Gnomad AMR exome

AF:

0.158

Gnomad ASJ exome

AF:

0.0552

Gnomad EAS exome

AF:

0.213

Gnomad FIN exome

AF:

0.122

Gnomad NFE exome

AF:

0.0795

Gnomad OTH exome

AF:

0.0868

GnomAD4 exome

AF:

0.0868

AC:

126833

AN:

1460960

Hom.:

6264

Cov.:

AF XY:

0.0855

AC XY:

62132

AN XY:

726792

show subpopulations

African (AFR)

AF:

0.0442

AC:

1476

AN:

33384

American (AMR)

AF:

0.151

AC:

6688

AN:

44416

Ashkenazi Jewish (ASJ)

AF:

0.0551

AC:

1437

AN:

26092

East Asian (EAS)

AF:

0.202

AC:

8017

AN:

39696

South Asian (SAS)

AF:

0.0709

AC:

6100

AN:

86046

European-Finnish (FIN)

AF:

0.121

AC:

6460

AN:

53414

Middle Eastern (MID)

AF:

0.0482

AC:

278

AN:

5768

European-Non Finnish (NFE)

AF:

0.0821

AC:

91247

AN:

1111810

Other (OTH)

AF:

0.0850

AC:

5130

AN:

60334

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.483

Heterozygous variant carriers

6140

12280

18420

24560

30700

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

3500

7000

10500

14000

17500

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0790

AC:

12018

AN:

152158

Hom.:

529

Cov.:

AF XY:

0.0814

AC XY:

6055

AN XY:

74368

show subpopulations

African (AFR)

AF:

0.0455

AC:

1888

AN:

41516

American (AMR)

AF:

0.106

AC:

1615

AN:

15288

Ashkenazi Jewish (ASJ)

AF:

0.0522

AC:

181

AN:

3470

East Asian (EAS)

AF:

0.200

AC:

1032

AN:

5172

South Asian (SAS)

AF:

0.0800

AC:

386

AN:

4824

European-Finnish (FIN)

AF:

0.121

AC:

1279

AN:

10576

Middle Eastern (MID)

AF:

0.0646

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0799

AC:

5435

AN:

67992

Other (OTH)

AF:

0.0747

AC:

158

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

553

1105

1658

2210

2763

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

140

280

420

560

700

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0763

Hom.:

610

Bravo

AF:

0.0797

TwinsUK

AF:

0.0898

AC:

333

ALSPAC

AF:

0.0804

AC:

310

ESP6500AA

AF:

0.0495

AC:

218

ESP6500EA

AF:

0.0737

AC:

634

ExAC

AF:

0.0974

AC:

11830

Asia WGS

AF:

0.130

AC:

453

AN:

3478

EpiCase

AF:

0.0736

EpiControl

AF:

0.0739

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.078

BayesDel_addAF

Benign

-0.58

BayesDel_noAF

Benign

-0.47

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.25

T;.;.

Eigen

Benign

-0.44

Eigen_PC

Benign

-0.41

FATHMM_MKL

Uncertain

0.79

LIST_S2

Benign

0.67

T;.;T

MetaRNN

Benign

0.00096

T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Uncertain

2.7

M;.;.

PhyloP100

1.3

PrimateAI

Benign

0.43

PROVEAN

Benign

-0.98

N;.;N

REVEL

Benign

0.046

Sift

Uncertain

0.0020

D;.;D

Sift4G

Uncertain

0.031

D;T;T

Polyphen

0.0030

B;.;.

Vest4

0.066

MPC

0.033

ClinPred

0.031

GERP RS

3.7

Varity_R

0.19

gMVP

0.70

Mutation Taster

=98/2

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over