rs148864662

Variant names:

• chr12-114408224-C-A
• ENST00000310346.8:c.-449G>T

Your query was ambiguous. Multiple possible variants found:

• chr12-114408224-C-A
• chr12-114408224-C-G

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_Strong BS2

The NM_000192.3(TBX5):​c.-449G>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000012 in 832,896 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.000012 (0 hom.)
• Consequence: TBX5 NM_000192.3 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0190

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]

TBX5-AS1 (HGNC:27402): (TBX5 antisense RNA 1)

ACMG classification

Verdict is Benign. Variant got -8 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.75).
• BS2: High AC in GnomAdExome4 at 10 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TBX5	NM_000192.3	c.-449G>T		5_prime_UTR_variant	Exon 1 of 9		NP_000183.2
TBX5-AS1	NR_038440.1	n.30C>A		non_coding_transcript_exon_variant	Exon 1 of 3
TBX5	NM_080717.4	c.-414G>T		upstream_gene_variant			NP_542448.1
TBX5	XM_017019912.2	c.-1886G>T		upstream_gene_variant			XP_016875401.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TBX5	ENST00000310346.8	c.-449G>T		5_prime_UTR_variant	Exon 1 of 9	1		ENSP00000309913.4
TBX5	ENST00000349716.9	c.-414G>T		5_prime_UTR_variant	Exon 1 of 8	1		ENSP00000337723.5
TBX5-AS1	ENST00000528549.3	n.91C>A		non_coding_transcript_exon_variant	Exon 1 of 3	1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.0000120 AC: 10 AN: 832896 Hom.: 0 Cov.: 28 AF XY: 0.00000780 AC XY: 3 AN XY: 384630

Gnomad4 AFR exome AF: 0.0000634

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: 0.0000118

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.75
CADD	Benign	5.7
DANN	Benign	0.80

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: chr12-114846029;