12-114358479-G-T

Position:

• chr12-114358479-G-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_181486.4(TBX5):​c.983-2373C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0945 in 152,082 control chromosomes in the GnomAD database, including 821 homozygotes. 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: 𝑓 0.094 (821 hom., cov: 32)
• Consequence: TBX5 NM_181486.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.158

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.167 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TBX5	NM_181486.4	c.983-2373C>A		intron_variant		ENST00000405440.7	NP_852259.1
TBX5	NM_000192.3	c.983-2373C>A		intron_variant			NP_000183.2
TBX5	NM_080717.4	c.833-2373C>A		intron_variant			NP_542448.1
TBX5	XM_017019912.2	c.1031-2373C>A		intron_variant			XP_016875401.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TBX5	ENST00000405440.7	c.983-2373C>A		intron_variant		1	NM_181486.4	ENSP00000384152	P1
TBX5	ENST00000310346.8	c.983-2373C>A		intron_variant		1		ENSP00000309913	P1
TBX5	ENST00000349716.9	c.833-2373C>A		intron_variant		1		ENSP00000337723

Frequencies

GnomAD3 genomes AF: 0.0946 AC: 14369 AN: 151964 Hom.: 825 Cov.: 32

Gnomad AFR AF: 0.0815

Gnomad AMI AF: 0.0406

Gnomad AMR AF: 0.151

Gnomad ASJ AF: 0.175

Gnomad EAS AF: 0.137

Gnomad SAS AF: 0.178

Gnomad FIN AF: 0.0848

Gnomad MID AF: 0.169

Gnomad NFE AF: 0.0782

Gnomad OTH AF: 0.109

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

GnomAD4 genome AF: 0.0945 AC: 14369 AN: 152082 Hom.: 821 Cov.: 32 AF XY: 0.0964 AC XY: 7169 AN XY: 74352

Gnomad4 AFR AF: 0.0814

Gnomad4 AMR AF: 0.150

Gnomad4 ASJ AF: 0.175

Gnomad4 EAS AF: 0.137

Gnomad4 SAS AF: 0.177

Gnomad4 FIN AF: 0.0848

Gnomad4 NFE AF: 0.0782

Gnomad4 OTH AF: 0.113

Alfa AF: 0.0889 Hom.: 1280

Bravo AF: 0.0992

Asia WGS AF: 0.180 AC: 626 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	1.5
DANN	Benign	0.55

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: rs10507246; hg19: chr12-114796284;