rs28936696

Variant names:

• chr17-61483470-A-C
• NM_001321120.2:c.1595A>C

Your query was ambiguous. Multiple possible variants found:

• chr17-61483470-A-C
• chr17-61483470-A-G

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001321120.2(TBX4):​c.1595A>C​(p.Gln532Pro) variant causes a missense change. The variant allele was found at a frequency of 0.000000684 in 1,461,894 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: 6.8e-7 (0 hom.)
• Consequence: TBX4 NM_001321120.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.44

Genes affected

TBX4 (HGNC:11603): (T-box transcription factor 4) 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 the human homolog of mouse Tbx4, which is closely linked to Tbx2 on mouse chromosome 11. Similarly this gene, like TBX2, maps to human chromosome 17. Expression studies in mouse and chicken show that Tbx4 is expressed in developing hindlimb, but not in forelimb buds, suggesting a role for this gene in regulating limb development and specification of limb identity. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.29846185).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TBX4	NM_001321120.2	c.1595A>C	p.Gln532Pro	missense_variant	Exon 9 of 9	ENST00000644296.1	NP_001308049.1
TBX4	NM_018488.3	c.1592A>C	p.Gln531Pro	missense_variant	Exon 8 of 8		NP_060958.2
TBX4	XM_011525490.3	c.1784A>C	p.Gln595Pro	missense_variant	Exon 9 of 9		XP_011523792.1
TBX4	XM_011525491.3	c.1781A>C	p.Gln594Pro	missense_variant	Exon 9 of 9		XP_011523793.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TBX4	ENST00000644296.1	c.1595A>C	p.Gln532Pro	missense_variant	Exon 9 of 9		NM_001321120.2	ENSP00000495986.1
TBX4	ENST00000240335.1	c.1592A>C	p.Gln531Pro	missense_variant	Exon 8 of 8	1		ENSP00000240335.1
TBX4	ENST00000642491.1	c.1595A>C	p.Gln532Pro	missense_variant	Exon 8 of 8			ENSP00000495714.1
TBX4	ENST00000589449.5	n.*100A>C		downstream_gene_variant		1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461894 Hom.: 0 Cov.: 35 AF XY: 0.00000138 AC XY: 1 AN XY: 727248

Gnomad4 AFR exome AF: 0.00

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: 8.99e-7

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
AlphaMissense	Benign	0.061
BayesDel_addAF	Uncertain	0.098	D
BayesDel_noAF	Benign	-0.10
CADD	Benign	23
DANN	Uncertain	0.99
DEOGEN2	Benign	0.30	.;.;T;.
Eigen	Benign	0.040
Eigen_PC	Benign	0.18
FATHMM_MKL	Uncertain	0.85	D
LIST_S2	Benign	0.79	.;.;T;T
M_CAP	Uncertain	0.12	D
MetaRNN	Benign	0.30	T;T;T;T
MetaSVM	Uncertain	-0.026	T
MutationAssessor	Benign	1.4	.;.;L;.
PrimateAI	Uncertain	0.55	T
PROVEAN	Benign	-0.25	N;.;N;.
REVEL	Uncertain	0.34
Sift	Uncertain	0.010	D;.;D;.
Sift4G	Pathogenic	0.0	D;.;D;.
Polyphen		0.0010	.;.;B;.
Vest4		0.31
MutPred		0.39		.;.;Gain of glycosylation at S529 (P = 0.066);.;
MVP		0.81
MPC		0.50
ClinPred		0.80	D
GERP RS		5.2
Varity_R		0.22
gMVP		0.73

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: chr17-59560831;