rs2278022

chr16-81043216-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

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. 12/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

• Frequency:
  • Genomes: 𝑓 0.079 (529 hom., cov: 32)
  • Exomes 𝑓: 0.087 (6264 hom.)
• Consequence: ATMIN NM_015251.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.27

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]

ACMG classification

Verdict is Benign. Variant got -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/exons	MANE	UniProt
ATMIN	NM_015251.3	c.718T>C	p.Ser240Pro	missense_variant	4/4	ENST00000299575.5
ATMIN	NM_001300728.2	c.250T>C	p.Ser84Pro	missense_variant	4/4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ATMIN	ENST00000299575.5	c.718T>C	p.Ser240Pro	missense_variant	4/4	1	NM_015251.3	P1
ATMIN	ENST00000564241.5	c.250T>C	p.Ser84Pro	missense_variant	4/4	1
ATMIN	ENST00000566488.1	c.250T>C	p.Ser84Pro	missense_variant	3/3	1
ATMIN	ENST00000539819.5	n.476T>C		non_coding_transcript_exon_variant	3/3	2

Frequencies

GnomAD3 genomes AF: 0.0790 AC: 12015 AN: 152038 Hom.: 528 Cov.: 32

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

GnomAD3 exomes AF: 0.100 AC: 25109 AN: 250652 Hom.: 1575 AF XY: 0.0958 AC XY: 12982 AN XY: 135498

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 SAS exome AF: 0.0730

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.: 31 AF XY: 0.0855 AC XY: 62132 AN XY: 726792

Gnomad4 AFR exome AF: 0.0442

Gnomad4 AMR exome AF: 0.151

Gnomad4 ASJ exome AF: 0.0551

Gnomad4 EAS exome AF: 0.202

Gnomad4 SAS exome AF: 0.0709

Gnomad4 FIN exome AF: 0.121

Gnomad4 NFE exome AF: 0.0821

Gnomad4 OTH exome AF: 0.0850

GnomAD4 genome AF: 0.0790 AC: 12018 AN: 152158 Hom.: 529 Cov.: 32 AF XY: 0.0814 AC XY: 6055 AN XY: 74368

Gnomad4 AFR AF: 0.0455

Gnomad4 AMR AF: 0.106

Gnomad4 ASJ AF: 0.0522

Gnomad4 EAS AF: 0.200

Gnomad4 SAS AF: 0.0800

Gnomad4 FIN AF: 0.121

Gnomad4 NFE AF: 0.0799

Gnomad4 OTH AF: 0.0747

Alfa AF: 0.0751 Hom.: 369

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	T
BayesDel_noAF	Benign	-0.47
Cadd	Benign	15
Dann	Uncertain	0.99
DEOGEN2	Benign	0.25	T;.;.
Eigen	Benign	-0.44
Eigen_PC	Benign	-0.41
FATHMM_MKL	Uncertain	0.79	D
LIST_S2	Benign	0.67	T;.;T
MetaRNN	Benign	0.00096	T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.7	M;.;.
MutationTaster	Benign	1.0	P;P;P
PrimateAI	Benign	0.43	T
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	T
GERP RS		3.7
Varity_R		0.19
gMVP		0.70

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

Other links and lift over

dbSNP: rs2278022; hg19: chr16-81076821; COSMIC: COSV55145414; COSMIC: COSV55145414;