rs886038791

Variant names:

• chr22-19760999-CCCGCCG-C
• rs886038791
• NM_001379200.1:c.167_172delCGCCGC

Your query was ambiguous. Multiple possible variants found:

• chr22-19760999-CCCGCCG-C
• chr22-19760999-CCCGCCG-CCCG
• chr22-19760999-CCCGCCG-CCCGCCGCCG
• chr22-19760999-CCCGCCG-CCCGCCGCCGCCG

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 0P and 5B. BP3 BS2

The NM_001379200.1(TBX1):​c.167_172delCGCCGC​(p.Pro56_Pro57del) variant causes a disruptive inframe deletion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000182 in 933,998 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000014 (0 hom., cov: 31)
  • Exomes 𝑓: 0.000019 (0 hom.)
• Consequence: TBX1 NM_001379200.1 disruptive_inframe_deletion
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.41
• Publications: 0 publications found

Genes affected

TBX1 (HGNC:11592): (T-box transcription factor 1) This gene is a member of a phylogenetically conserved family of genes that share a common DNA-binding domain, the T-box. T-box genes encode transcription factors involved in the regulation of developmental processes. This gene product shares 98% amino acid sequence identity with the mouse ortholog. DiGeorge syndrome (DGS)/velocardiofacial syndrome (VCFS), a common congenital disorder characterized by neural-crest-related developmental defects, has been associated with deletions of chromosome 22q11.2, where this gene has been mapped. Studies using mouse models of DiGeorge syndrome suggest a major role for this gene in the molecular etiology of DGS/VCFS. Several alternatively spliced transcript variants encoding different isoforms have been described for this gene. [provided by RefSeq, Jul 2008]

TBX1 Gene-Disease associations (from GenCC):

• conotruncal heart malformations

  Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics
• DiGeorge syndrome

  Inheritance: AD Classification: DEFINITIVE Submitted by: G2P
• velocardiofacial syndrome

  Inheritance: AD Classification: STRONG Submitted by: Ambry Genetics
• 22q11.2 deletion syndrome

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Likely_benign. The variant received -5 ACMG points.

• BP3: Nonframeshift variant in repetitive region in NM_001379200.1
• BS2: High AC in GnomAdExome4 at 15 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001379200.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TBX1	NM_001379200.1	MANE Select	c.167_172delCGCCGC	p.Pro56_Pro57del	disruptive_inframe_deletion	Exon 1 of 7	NP_001366129.1	A0A3B3IS18
	TBX1	NM_080647.1		c.140_145delCGCCGC	p.Pro47_Pro48del	disruptive_inframe_deletion	Exon 3 of 9	NP_542378.1	O43435-3
	TBX1	NM_080646.2		c.140_145delCGCCGC	p.Pro47_Pro48del	disruptive_inframe_deletion	Exon 3 of 9	NP_542377.1	O43435-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TBX1	ENST00000649276.2	MANE Select	c.167_172delCGCCGC	p.Pro56_Pro57del	disruptive_inframe_deletion	Exon 1 of 7	ENSP00000497003.1	A0A3B3IS18
	TBX1	ENST00000332710.8	TSL:1	c.140_145delCGCCGC	p.Pro47_Pro48del	disruptive_inframe_deletion	Exon 3 of 9	ENSP00000331791.4	O43435-3
	TBX1	ENST00000329705.11	TSL:1	c.140_145delCGCCGC	p.Pro47_Pro48del	disruptive_inframe_deletion	Exon 3 of 9	ENSP00000331176.7	O43435-1

Frequencies

GnomAD3 genomes AF: 0.0000137 AC: 2 AN: 145488 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000305

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.0000190 AC: 15 AN: 788510 Hom.: 0 AF XY: 0.0000246 AC XY: 9 AN XY: 365230

African (AFR) AF: 0.0000674 AC: 1 AN: 14846

American (AMR) AF: 0.00 AC: 0 AN: 932

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 4876

East Asian (EAS) AF: 0.000298 AC: 1 AN: 3358

South Asian (SAS) AF: 0.00 AC: 0 AN: 16374

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 262

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 1552

European-Non Finnish (NFE) AF: 0.0000180 AC: 13 AN: 720542

Other (OTH) AF: 0.00 AC: 0 AN: 25768

GnomAD4 genome AF: 0.0000137 AC: 2 AN: 145488 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 70692

African (AFR) AF: 0.00 AC: 0 AN: 40636

American (AMR) AF: 0.00 AC: 0 AN: 14678

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3380

East Asian (EAS) AF: 0.00 AC: 0 AN: 4970

South Asian (SAS) AF: 0.00 AC: 0 AN: 4784

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 8282

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 298

European-Non Finnish (NFE) AF: 0.0000305 AC: 2 AN: 65558

Other (OTH) AF: 0.00 AC: 0 AN: 1998

Alfa AF: 0.00 Hom.: 0

ClinVar

ClinVar submissions as Germline

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	DiGeorge syndrome (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		1.4
Mutation Taster		=179/21	polymorphism

Splicing

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

Other links and lift over

dbSNP: rs886038791; hg19: chr22-19748522;