12-114354773-TGGCA-CCAGCTGAATAAGAGCCCAGCATCTTATTC

Position:

• chr12-114354773-TGGCA-CCAGCTGAATAAGAGCCCAGCATCTTATTC

Variant summary

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

The NM_181486.4(TBX5):​c.*755_*759delinsGAATAAGATGCTGGGCTCTTATTCAGCTGG variant causes a 3 prime UTR 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 Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: TBX5 NM_181486.4 3_prime_UTR
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.44

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 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/exons	MANE	Protein	UniProt
TBX5	NM_181486.4	c.*755_*759delinsGAATAAGATGCTGGGCTCTTATTCAGCTGG		3_prime_UTR_variant	9/9	ENST00000405440.7	NP_852259.1
TBX5	NM_000192.3	c.*755_*759delinsGAATAAGATGCTGGGCTCTTATTCAGCTGG		3_prime_UTR_variant	9/9		NP_000183.2
TBX5	NM_080717.4	c.*755_*759delinsGAATAAGATGCTGGGCTCTTATTCAGCTGG		3_prime_UTR_variant	8/8		NP_542448.1
TBX5	XM_017019912.2	c.*755_*759delinsGAATAAGATGCTGGGCTCTTATTCAGCTGG		3_prime_UTR_variant	9/9		XP_016875401.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TBX5	ENST00000405440.7	c.*755_*759delinsGAATAAGATGCTGGGCTCTTATTCAGCTGG		3_prime_UTR_variant	9/9	1	NM_181486.4	ENSP00000384152	P1
TBX5	ENST00000310346.8	c.*755_*759delinsGAATAAGATGCTGGGCTCTTATTCAGCTGG		3_prime_UTR_variant	9/9	1		ENSP00000309913	P1
TBX5	ENST00000349716.9	c.*755_*759delinsGAATAAGATGCTGGGCTCTTATTCAGCTGG		3_prime_UTR_variant	8/8	1		ENSP00000337723

Frequencies

GnomAD3 genomes Cov.: 32

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

Holt-Oram syndrome Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

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Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs886048992; hg19: chr12-114792578;