16-10480939-C-T

Variant names:

• chr16-10480939-C-T
• rs9932051
• NM_001393719.1:c.1610C>T

Variant summary

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

The NM_001393719.1(ATF7IP2):​c.1610C>T​(p.Thr537Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0354 in 1,610,966 control chromosomes in the GnomAD database, including 2,394 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/15 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 the same amino acid substitution has been previously reported as Likely benign in UniProt.

• Frequency:
  • Genomes: 𝑓 0.070 (735 hom., cov: 30)
  • Exomes 𝑓: 0.032 (1659 hom.)
• Consequence: ATF7IP2 NM_001393719.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.944

Genes affected

ATF7IP2 (HGNC:20397): (activating transcription factor 7 interacting protein 2) Predicted to be located in nucleus. [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=0.001392901).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.167 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ATF7IP2	NM_001393719.1	c.1610C>T	p.Thr537Ile	missense_variant	Exon 13 of 14	ENST00000562102.6	NP_001380648.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ATF7IP2	ENST00000562102.6	c.1610C>T	p.Thr537Ile	missense_variant	Exon 13 of 14	4	NM_001393719.1	ENSP00000457731.2

Frequencies

GnomAD3 genomes AF: 0.0702 AC: 10669 AN: 152002 Hom.: 725 Cov.: 30

Gnomad AFR AF: 0.170

Gnomad AMI AF: 0.00219

Gnomad AMR AF: 0.0357

Gnomad ASJ AF: 0.0597

Gnomad EAS AF: 0.132

Gnomad SAS AF: 0.0951

Gnomad FIN AF: 0.0102

Gnomad MID AF: 0.0285

Gnomad NFE AF: 0.0221

Gnomad OTH AF: 0.0527

GnomAD3 exomes AF: 0.0477 AC: 11995 AN: 251372 Hom.: 578 AF XY: 0.0458 AC XY: 6226 AN XY: 135854

Gnomad AFR exome AF: 0.178

Gnomad AMR exome AF: 0.0200

Gnomad ASJ exome AF: 0.0559

Gnomad EAS exome AF: 0.118

Gnomad SAS exome AF: 0.0890

Gnomad FIN exome AF: 0.00979

Gnomad NFE exome AF: 0.0220

Gnomad OTH exome AF: 0.0404

GnomAD4 exome AF: 0.0317 AC: 46306 AN: 1458846 Hom.: 1659 Cov.: 30 AF XY: 0.0327 AC XY: 23762 AN XY: 725928

Gnomad4 AFR exome AF: 0.172

Gnomad4 AMR exome AF: 0.0219

Gnomad4 ASJ exome AF: 0.0577

Gnomad4 EAS exome AF: 0.138

Gnomad4 SAS exome AF: 0.0876

Gnomad4 FIN exome AF: 0.0102

Gnomad4 NFE exome AF: 0.0194

Gnomad4 OTH exome AF: 0.0455

GnomAD4 genome AF: 0.0704 AC: 10712 AN: 152120 Hom.: 735 Cov.: 30 AF XY: 0.0701 AC XY: 5214 AN XY: 74354

Gnomad4 AFR AF: 0.171

Gnomad4 AMR AF: 0.0356

Gnomad4 ASJ AF: 0.0597

Gnomad4 EAS AF: 0.133

Gnomad4 SAS AF: 0.0945

Gnomad4 FIN AF: 0.0102

Gnomad4 NFE AF: 0.0221

Gnomad4 OTH AF: 0.0583

Alfa AF: 0.0323 Hom.: 325

Bravo AF: 0.0742

TwinsUK AF: 0.0243 AC: 90

ALSPAC AF: 0.0221 AC: 85

ESP6500AA AF: 0.177 AC: 778

ESP6500EA AF: 0.0238 AC: 205

ExAC AF: 0.0523 AC: 6347

Asia WGS AF: 0.156 AC: 540 AN: 3478

EpiCase AF: 0.0266

EpiControl AF: 0.0249

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.067
BayesDel_addAF	Benign	-0.69	T
BayesDel_noAF	Benign	-0.72
CADD	Benign	0.12
DANN	Benign	0.56
Eigen	Benign	-1.4
Eigen_PC	Benign	-1.5
FATHMM_MKL	Benign	0.0076	N
LIST_S2	Benign	0.39	.;T
MetaRNN	Benign	0.0014	T;T
MetaSVM	Benign	-0.96	T
PROVEAN	Benign	0.37	N;N
REVEL	Benign	0.071
Sift	Pathogenic	0.0	D;D
Sift4G	Benign	0.56	T;T
Polyphen		0.0010	B;B
Vest4		0.32
ClinPred		0.0062	T
GERP RS		-6.5

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs9932051; hg19: chr16-10574796; COSMIC: COSV61094093;