Variant chr8-38788817-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The ENST00000317827.9(TACC1):c.275A>G(p.Gln92Arg) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000853 in 1,595,068 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/23 in silico tools predict a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000046 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000089 ( 0 hom. )

Consequence

TACC1
ENST00000317827.9 missense, splice_region

Scores

Splicing: ADA: 0.07960

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.19

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:

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ACMG classification

Classification made for transcript

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=0.12423515).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TACC1	NM_006283.3 linkuse as main transcript	c.275A>G	p.Gln92Arg	missense_variant, splice_region_variant	2/13	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.275A>G	p.Gln92Arg	missense_variant, splice_region_variant	2/13	1	NM_006283.3	ENSP00000321703.4		O75410-1

Frequencies

GnomAD3 genomes

AF:

0.0000460

AC:

AN:

152238

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:

0.0000882

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000302

AC:

AN:

231410

Hom.:

AF XY:

0.0000400

AC XY:

AN XY:

125038

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000650

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000894

AC:

129

AN:

1442830

Hom.:

Cov.:

AF XY:

0.0000949

AC XY:

AN XY:

716862

show subpopulations

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:

0.000115

Gnomad4 OTH exome

AF:

0.0000335

GnomAD4 genome

AF:

0.0000460

AC:

AN:

152238

Hom.:

Cov.:

AF XY:

0.0000134

AC XY:

AN XY:

74380

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:

0.0000882

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000772

Hom.:

Bravo

AF:

0.0000340

ExAC

AF:

0.0000247

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

Jan 03, 2024

The c.275A>G (p.Q92R) alteration is located in exon 2 (coding exon 2) of the TACC1 gene. This alteration results from a A to G substitution at nucleotide position 275, causing the glutamine (Q) at amino acid position 92 to be replaced by an arginine (R). 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

0.080

BayesDel_addAF

Benign

-0.24

BayesDel_noAF

Benign

-0.41

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.027

.;.;T;T;T

Eigen

Benign

0.14

Eigen_PC

Benign

0.19

FATHMM_MKL

Benign

0.76

LIST_S2

Benign

0.80

T;T;T;T;T

M_CAP

Benign

0.0073

MetaRNN

Benign

0.12

T;T;T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Uncertain

2.5

.;.;.;.;M

MutationTaster

Benign

0.59

D;D;D;D;D;D;D;D;D;D

PrimateAI

Benign

0.40

PROVEAN

Benign

-1.4

.;N;N;N;N

REVEL

Benign

0.11

Sift

Uncertain

0.0040

.;D;D;D;D

Sift4G

Benign

0.34

T;T;T;T;T

Polyphen

0.99, 0.92

.;D;.;.;P

Vest4

0.19

MVP

0.43

MPC

0.23

ClinPred

0.14

GERP RS

4.2

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

2.7

Varity_R

0.23

gMVP

0.13

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.080

dbscSNV1_RF

Benign

0.31

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