rs200073406

Positions:

• chr12-114355937-C-G
• chr12-114355937-C-T

Variant summary

Our verdict is Likely benign. Variant got -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP7

The NM_181486.4(TBX5):​c.1152G>C​(p.Ala384Ala) 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: 33)
• Consequence: TBX5 NM_181486.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.42

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 -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.67).
• BP7: Synonymous conserved (PhyloP=-2.42 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TBX5	NM_181486.4	c.1152G>C	p.Ala384Ala	synonymous_variant	9/9	ENST00000405440.7	NP_852259.1
TBX5	NM_000192.3	c.1152G>C	p.Ala384Ala	synonymous_variant	9/9		NP_000183.2
TBX5	NM_080717.4	c.1002G>C	p.Ala334Ala	synonymous_variant	8/8		NP_542448.1
TBX5	XM_017019912.2	c.1200G>C	p.Ala400Ala	synonymous_variant	9/9		XP_016875401.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TBX5	ENST00000405440.7	c.1152G>C	p.Ala384Ala	synonymous_variant	9/9	1	NM_181486.4	ENSP00000384152.3
TBX5	ENST00000310346.8	c.1152G>C	p.Ala384Ala	synonymous_variant	9/9	1		ENSP00000309913.4
TBX5	ENST00000349716.9	c.1002G>C	p.Ala334Ala	synonymous_variant	8/8	1		ENSP00000337723.5

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.67
CADD	Benign	0.48
DANN	Benign	0.68

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: rs200073406; hg19: chr12-114793742;