8-38787721-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_006283.3(TACC1):c.139G>A(p.Glu47Lys) variant causes a missense change. The variant allele was found at a frequency of 0.00000358 in 1,395,680 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000036 (0 hom.)
• Consequence: TACC1 NM_006283.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.26

Genes affected

TACC1 (HGNC:11522): (transforming acidic coiled-coil containing protein 1) This locus may represent a breast cancer candidate gene. It is located close to FGFR1 on a region of chromosome 8 that is amplified in some breast cancers. Several transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jun 2017]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.21319556).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TACC1	NM_006283.3	c.139G>A	p.Glu47Lys	missense_variant	1/13	ENST00000317827.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TACC1	ENST00000317827.9	c.139G>A	p.Glu47Lys	missense_variant	1/13	1	NM_006283.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.00000628 AC: 1 AN: 159192 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 87230

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000918

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000358 AC: 5 AN: 1395680 Hom.: 0 Cov.: 32 AF XY: 0.00000289 AC XY: 2 AN XY: 691542

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000836

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 9.20e-7

Gnomad4 OTH exome AF: 0.0000172

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000756

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Feb 07, 2023

The c.139G>A (p.E47K) alteration is located in exon 1 (coding exon 1) of the TACC1 gene. This alteration results from a G to A substitution at nucleotide position 139, causing the glutamic acid (E) at amino acid position 47 to be replaced by a lysine (K). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.46
BayesDel_addAF	Uncertain	0.037	T
BayesDel_noAF	Benign	-0.18
Cadd	Pathogenic	27
Dann	Uncertain	1.0
DEOGEN2	Benign	0.046	T;T;.
Eigen	Benign	0.17
Eigen_PC	Uncertain	0.25
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Uncertain	0.93	D;D;T
M_CAP	Benign	0.022	T
MetaRNN	Benign	0.21	T;T;T
MetaSVM	Benign	-0.82	T
MutationTaster	Benign	0.99	D;D;D;D;D;D;D;D;N
PrimateAI	Pathogenic	0.84	D
PROVEAN	Benign	-1.6	N;N;N
REVEL	Benign	0.12
Sift	Uncertain	0.0090	D;D;T
Sift4G	Benign	0.17	T;T;T
Polyphen		0.86, 0.0050	.;P;B
Vest4		0.31, 0.28
MutPred		0.14		Gain of ubiquitination at E47 (P = 0.0031);Gain of ubiquitination at E47 (P = 0.0031);Gain of ubiquitination at E47 (P = 0.0031);
MVP		0.54
MPC		0.39
ClinPred		0.81	D
GERP RS		4.8
Varity_R		0.27
gMVP		0.15

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: rs865921018; hg19: chr8-38645239;