12-114354146-GA-G

Position:

• chr12-114354146-GA-G

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_181486.4(TBX5):​c.*1385del variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.79 (47525 hom., cov: 0)
  • Exomes 𝑓: 0.76 (123 hom.)
• Consequence: TBX5 NM_181486.4 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• 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 Benign. Variant got -10 ACMG points.

• BP6: Variant 12-114354146-GA-G is Benign according to our data. Variant chr12-114354146-GA-G is described in ClinVar as [Benign]. Clinvar id is 307269.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.888 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TBX5	NM_181486.4	c.*1385del		3_prime_UTR_variant	9/9	ENST00000405440.7
TBX5	NM_000192.3	c.*1385del		3_prime_UTR_variant	9/9
TBX5	NM_080717.4	c.*1385del		3_prime_UTR_variant	8/8
TBX5	XM_017019912.2	c.*1385del		3_prime_UTR_variant	9/9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TBX5	ENST00000405440.7	c.*1385del		3_prime_UTR_variant	9/9	1	NM_181486.4	P1
TBX5	ENST00000310346.8	c.*1385del		3_prime_UTR_variant	9/9	1		P1
TBX5	ENST00000349716.9	c.*1385del		3_prime_UTR_variant	8/8	1

Frequencies

GnomAD3 genomes AF: 0.794 AC: 119394 AN: 150330 Hom.: 47491 Cov.: 0

Gnomad AFR AF: 0.779

Gnomad AMI AF: 0.848

Gnomad AMR AF: 0.706

Gnomad ASJ AF: 0.784

Gnomad EAS AF: 0.910

Gnomad SAS AF: 0.771

Gnomad FIN AF: 0.780

Gnomad MID AF: 0.788

Gnomad NFE AF: 0.818

Gnomad OTH AF: 0.786

GnomAD4 exome AF: 0.762 AC: 329 AN: 432 Hom.: 123 Cov.: 0 AF XY: 0.765 AC XY: 199 AN XY: 260

Gnomad4 FIN exome AF: 0.763

Gnomad4 NFE exome AF: 0.500

Gnomad4 OTH exome AF: 0.750

GnomAD4 genome AF: 0.794 AC: 119470 AN: 150436 Hom.: 47525 Cov.: 0 AF XY: 0.792 AC XY: 58088 AN XY: 73348

Gnomad4 AFR AF: 0.779

Gnomad4 AMR AF: 0.705

Gnomad4 ASJ AF: 0.784

Gnomad4 EAS AF: 0.910

Gnomad4 SAS AF: 0.771

Gnomad4 FIN AF: 0.780

Gnomad4 NFE AF: 0.818

Gnomad4 OTH AF: 0.787

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Holt-Oram syndrome Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

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;