Variant 8-38787709-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The ENST00000317827.9(TACC1):c.127G>T(p.Asp43Tyr) variant causes a missense change. The variant allele was found at a frequency of 0.0000508 in 1,536,610 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: 𝑓 0.000079 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000048 ( 0 hom. )

Consequence

TACC1
ENST00000317827.9 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.15

Variant links:

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]

TACC1 links:

TACC1 (HGNC:):

TACC1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.061688334).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TACC1	NM_006283.3 linkuse as main transcript	c.127G>T	p.Asp43Tyr	missense_variant	1/13	ENST00000317827.9	NP_006274.2	O75410-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TACC1	ENST00000317827.9 linkuse as main transcript	c.127G>T	p.Asp43Tyr	missense_variant	1/13	1	NM_006283.3	ENSP00000321703.4		O75410-1

Frequencies

GnomAD3 genomes

AF:

0.0000789

AC:

AN:

152162

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000162

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000362

AC:

AN:

137954

Hom.:

AF XY:

0.0000263

AC XY:

AN XY:

76132

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000505

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000128

Gnomad NFE exome

AF:

0.0000502

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000477

AC:

AN:

1384448

Hom.:

Cov.:

AF XY:

0.0000467

AC XY:

AN XY:

684946

show subpopulations

Gnomad4 AFR exome

AF:

0.0000329

Gnomad4 AMR exome

AF:

0.0000315

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000252

Gnomad4 FIN exome

AF:

0.0000507

Gnomad4 NFE exome

AF:

0.0000546

Gnomad4 OTH exome

AF:

0.0000173

GnomAD4 genome

AF:

0.0000789

AC:

AN:

152162

Hom.:

Cov.:

AF XY:

0.0000404

AC XY:

AN XY:

74324

show subpopulations

Gnomad4 AFR

AF:

0.0000241

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000162

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000167

Hom.:

Bravo

AF:

0.0000869

ExAC

AF:

0.0000266

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 03, 2021

The c.127G>T (p.D43Y) alteration is located in exon 1 (coding exon 1) of the TACC1 gene. This alteration results from a G to T substitution at nucleotide position 127, causing the aspartic acid (D) at amino acid position 43 to be replaced by a tyrosine (Y). 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

Benign

0.25

BayesDel_addAF

Benign

-0.11

BayesDel_noAF

Benign

-0.22

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Benign

0.11

T;T;.

Eigen

Uncertain

0.65

Eigen_PC

Uncertain

0.61

FATHMM_MKL

Uncertain

0.94

LIST_S2

Uncertain

0.88

D;D;D

M_CAP

Uncertain

0.086

MetaRNN

Benign

0.062

T;T;T

MetaSVM

Benign

-0.54

MutationAssessor

Uncertain

2.4

.;M;M

MutationTaster

Benign

0.97

D;D;D;D;D;D;D;D;N

PrimateAI

Uncertain

0.75

PROVEAN

Pathogenic

-5.3

D;N;N

REVEL

Benign

0.16

Sift

Uncertain

0.0010

D;D;D

Sift4G

Uncertain

0.0040

D;D;D

Polyphen

1.0, 0.99

.;D;D

Vest4

0.42, 0.37

MutPred

0.14

Gain of phosphorylation at D43 (P = 0.0037);Gain of phosphorylation at D43 (P = 0.0037);Gain of phosphorylation at D43 (P = 0.0037);

MVP

0.69

MPC

0.39

ClinPred

0.87

GERP RS

4.8

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

2.8

Varity_R

0.28

gMVP

0.14

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over