chr12-114354146-GAA-G

Variant names:

• chr12-114354146-GAA-G
• rs35534655
• NM_181486.4:c.*1384_*1385delTT

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2

The NM_181486.4(TBX5):​c.*1384_*1385delTT variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.000073 (0 hom., cov: 0)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: TBX5 NM_181486.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.722

Genes affected

TBX5 (HGNC:11604): (T-box transcription factor 5) 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 is closely linked to related family member T-box 3 (ulnar mammary syndrome) on human chromosome 12. The encoded protein may play a role in heart development and specification of limb identity. Mutations in this gene have been associated with Holt-Oram syndrome, a developmental disorder affecting the heart and upper limbs. Several transcript variants encoding different isoforms have been described for this gene. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Likely_benign. Variant got -4 ACMG points.

• BS2: High AC in GnomAd4 at 11 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TBX5	NM_181486.4	c.*1384_*1385delTT		3_prime_UTR_variant	Exon 9 of 9	ENST00000405440.7	NP_852259.1
TBX5	NM_000192.3	c.*1384_*1385delTT		3_prime_UTR_variant	Exon 9 of 9		NP_000183.2
TBX5	NM_080717.4	c.*1384_*1385delTT		3_prime_UTR_variant	Exon 8 of 8		NP_542448.1
TBX5	XM_017019912.2	c.*1384_*1385delTT		3_prime_UTR_variant	Exon 9 of 9		XP_016875401.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TBX5	ENST00000405440	c.*1384_*1385delTT		3_prime_UTR_variant	Exon 9 of 9	1	NM_181486.4	ENSP00000384152.3
TBX5	ENST00000310346	c.*1384_*1385delTT		3_prime_UTR_variant	Exon 9 of 9	1		ENSP00000309913.4
TBX5	ENST00000349716	c.*1384_*1385delTT		3_prime_UTR_variant	Exon 8 of 8	1		ENSP00000337723.5

Frequencies

GnomAD3 genomes AF: 0.0000731 AC: 11 AN: 150406 Hom.: 0 Cov.: 0

Gnomad AFR AF: 0.0000980

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000664

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000389

Gnomad SAS AF: 0.000210

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000443

Gnomad OTH AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 432 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 260

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.0000731 AC: 11 AN: 150512 Hom.: 0 Cov.: 0 AF XY: 0.0000681 AC XY: 5 AN XY: 73388

Gnomad4 AFR AF: 0.0000977

Gnomad4 AMR AF: 0.0000663

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.000389

Gnomad4 SAS AF: 0.000211

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000443

Gnomad4 OTH AF: 0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

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

LitVar

Other links and lift over

dbSNP: rs35534655; hg19: chr12-114791951;