12-114366343-G-T

Variant summary

Our verdict is Likely benign. Variant got -1 ACMG points: 2P and 3B. PM2BP4_ModerateBP7

The NM_181486.4(TBX5):​c.804C>A​(p.Ala268Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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)

Consequence

TBX5
NM_181486.4 synonymous

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.08
Variant links:
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]

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -1 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.44).
BP7
Synonymous conserved (PhyloP=1.08 with no splicing effect.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
TBX5NM_181486.4 linkc.804C>A p.Ala268Ala synonymous_variant Exon 8 of 9 ENST00000405440.7 NP_852259.1 Q99593-1
TBX5NM_000192.3 linkc.804C>A p.Ala268Ala synonymous_variant Exon 8 of 9 NP_000183.2 Q99593-1
TBX5NM_080717.4 linkc.654C>A p.Ala218Ala synonymous_variant Exon 7 of 8 NP_542448.1 Q99593-3
TBX5XM_017019912.2 linkc.852C>A p.Ala284Ala synonymous_variant Exon 8 of 9 XP_016875401.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
TBX5ENST00000405440.7 linkc.804C>A p.Ala268Ala synonymous_variant Exon 8 of 9 1 NM_181486.4 ENSP00000384152.3 Q99593-1
TBX5ENST00000310346.8 linkc.804C>A p.Ala268Ala synonymous_variant Exon 8 of 9 1 ENSP00000309913.4 Q99593-1
TBX5ENST00000349716.9 linkc.654C>A p.Ala218Ala synonymous_variant Exon 7 of 8 1 ENSP00000337723.5 Q99593-3
TBX5ENST00000526441.1 linkc.804C>A p.Ala268Ala synonymous_variant Exon 7 of 7 1 ENSP00000433292.1 Q99593-2

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
Cov.:
32
GnomAD4 genome
Cov.:
32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.44
CADD
Benign
8.7
DANN
Benign
0.73

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

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs35110399; hg19: chr12-114804148; COSMIC: COSV100090560; API