rs1555895466

Variant names:

• chr22-19761162-A-G
• NM_001379200.1:c.319A>G

Your query was ambiguous. Multiple possible variants found:

• chr22-19761162-A-G
• chr22-19761162-A-T

Variant summary

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

The NM_001379200.1(TBX1):​c.319A>G​(p.Lys107Glu) variant causes a missense change. The variant allele was found at a frequency of 0.000000739 in 1,353,432 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 7.4e-7 (0 hom.)
• Consequence: TBX1 NM_001379200.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.19

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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TBX1	NM_001379200.1	c.319A>G	p.Lys107Glu	missense_variant	Exon 1 of 7	ENST00000649276.2	NP_001366129.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TBX1	ENST00000649276.2	c.319A>G	p.Lys107Glu	missense_variant	Exon 1 of 7		NM_001379200.1	ENSP00000497003.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 7.39e-7 AC: 1 AN: 1353432 Hom.: 0 Cov.: 31 AF XY: 0.00000148 AC XY: 1 AN XY: 673518

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 9.50e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.22
BayesDel_addAF	Uncertain	0.030	T
BayesDel_noAF	Benign	-0.19
CADD	Benign	21
DANN	Uncertain	0.98
DEOGEN2	Benign	0.20	.;T;.;.
Eigen	Uncertain	0.27
Eigen_PC	Uncertain	0.22
FATHMM_MKL	Uncertain	0.92	D
LIST_S2	Benign	0.53	T;T;T;T
M_CAP	Pathogenic	0.98	D
MetaRNN	Uncertain	0.49	T;T;T;T
MetaSVM	Uncertain	0.090	D
MutationAssessor	Benign	0.0	N;N;N;.
PrimateAI	Pathogenic	0.97	D
PROVEAN	Benign	-0.70	N;N;N;.
REVEL	Uncertain	0.41
Sift	Benign	0.047	D;T;T;.
Sift4G	Benign	0.18	T;T;T;.
Polyphen		0.99	.;D;.;.
Vest4		0.27
MutPred		0.34		Loss of MoRF binding (P = 0.0045);Loss of MoRF binding (P = 0.0045);Loss of MoRF binding (P = 0.0045);.;
MVP		0.57
MPC		0.74
ClinPred		0.81	D
GERP RS		3.3
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.6
Varity_R		0.30
gMVP		0.52

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr22-19748685;