chr22-19759559-G-TC

Position:

• chr22-19759559-G-TC

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP6_Moderate

The NM_080647.1(TBX1):​c.-85delGinsTC variant causes a splice region change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: not found (cov: 36)
• Consequence: TBX1 NM_080647.1 splice_region
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.611

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP6: Variant 22-19759559-G-TC is Benign according to our data. Variant chr22-19759559-G-TC is described in ClinVar as [Benign]. Clinvar id is 1220890.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TBX1	NM_080647.1	c.-85delGinsTC		splice_region_variant	2/9		NP_542378.1
TBX1	NM_080646.2	c.-85delGinsTC		splice_region_variant	2/9		NP_542377.1
TBX1	NM_005992.1	c.-85delGinsTC		splice_region_variant	2/10		NP_005983.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TBX1	ENST00000332710.8	c.-85delGinsTC		splice_region_variant	2/9	1		ENSP00000331791.4
TBX1	ENST00000329705.11	c.-85delGinsTC		splice_region_variant	2/9	1		ENSP00000331176.7
TBX1	ENST00000359500.7	c.-85delGinsTC		splice_region_variant	2/10	1		ENSP00000352483.3

Frequencies

GnomAD3 genomes Cov.: 36

GnomAD4 exome Cov.: 54

GnomAD4 genome Cov.: 36

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Mar 03, 2015

- -

Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr22-19747082;