12-14424441-TCTGGTGATGCCCCTTCTGGTGATGTGTCCC-T

Position:

• chr12-14424441-TCTGGTGATGCCCCTTCTGGTGATGTGTCCC-T

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM4 BP6_Moderate BS2

The NM_018179.5(ATF7IP):​c.538_567del​(p.Pro180_Ala189del) variant causes a inframe deletion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000588 in 1,613,580 control chromosomes in the GnomAD database, including 5 homozygotes. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.00069 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00058 (5 hom.)
• Consequence: ATF7IP NM_018179.5 inframe_deletion
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.51

Genes affected

ATF7IP (HGNC:20092): (activating transcription factor 7 interacting protein) ATF7IP is a multifunctional nuclear protein that associates with heterochromatin. It can act as a transcriptional coactivator or corepressor depending upon its binding partners (summary by Liu et al., 2009 [PubMed 19106100]).[supplied by OMIM, Nov 2010]

ACMG classification

Verdict is Likely_benign. Variant got -4 ACMG points.

• PM4: Nonframeshift variant in NON repetitive region in NM_018179.5.
• BP6: Variant 12-14424441-TCTGGTGATGCCCCTTCTGGTGATGTGTCCC-T is Benign according to our data. Variant chr12-14424441-TCTGGTGATGCCCCTTCTGGTGATGTGTCCC-T is described in ClinVar as [Likely_benign]. Clinvar id is 3025287.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Homozygotes in GnomAdExome4 at 5 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ATF7IP	NM_018179.5	c.538_567del	p.Pro180_Ala189del	inframe_deletion	2/15	ENST00000261168.9	NP_060649.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ATF7IP	ENST00000261168.9	c.538_567del	p.Pro180_Ala189del	inframe_deletion	2/15	5	NM_018179.5	ENSP00000261168	P5

Frequencies

GnomAD3 genomes AF: 0.000691 AC: 105 AN: 151888 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000524

Gnomad ASJ AF: 0.0159

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00228

Gnomad FIN AF: 0.000189

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.000397

Gnomad OTH AF: 0.000480

GnomAD3 exomes AF: 0.000665 AC: 167 AN: 251282 Hom.: 3 AF XY: 0.000781 AC XY: 106 AN XY: 135802

Gnomad AFR exome AF: 0.0000615

Gnomad AMR exome AF: 0.000289

Gnomad ASJ exome AF: 0.00411

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00144

Gnomad FIN exome AF: 0.000785

Gnomad NFE exome AF: 0.000422

Gnomad OTH exome AF: 0.000978

GnomAD4 exome AF: 0.000577 AC: 844 AN: 1461574 Hom.: 5 AF XY: 0.000666 AC XY: 484 AN XY: 727084

Gnomad4 AFR exome AF: 0.000179

Gnomad4 AMR exome AF: 0.000291

Gnomad4 ASJ exome AF: 0.00836

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00226

Gnomad4 FIN exome AF: 0.000861

Gnomad4 NFE exome AF: 0.000249

Gnomad4 OTH exome AF: 0.00118

GnomAD4 genome AF: 0.000691 AC: 105 AN: 152006 Hom.: 0 Cov.: 32 AF XY: 0.000754 AC XY: 56 AN XY: 74314

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.000524

Gnomad4 ASJ AF: 0.0159

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00229

Gnomad4 FIN AF: 0.000189

Gnomad4 NFE AF: 0.000397

Gnomad4 OTH AF: 0.000475

Alfa AF: 0.00197 Hom.: 0

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Dec 01, 2023

ATF7IP: PM4, BS2 -

Computational scores

Source: dbNSFP v4.3

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs564557542; hg19: chr12-14577375;