chr8-38787620-A-G

Position:

• chr8-38787620-A-G

Variant summary

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

The NM_006283.3(TACC1):​c.38A>G​(p.Gln13Arg) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: TACC1 NM_006283.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.17

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 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TACC1	NM_006283.3	c.38A>G	p.Gln13Arg	missense_variant	1/13	ENST00000317827.9	NP_006274.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TACC1	ENST00000317827.9	c.38A>G	p.Gln13Arg	missense_variant	1/13	1	NM_006283.3	ENSP00000321703.4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.00000666 AC: 1 AN: 150198 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 79918

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000430

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: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000378

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

Dec 03, 2024

The c.38A>G (p.Q13R) alteration is located in exon 1 (coding exon 1) of the TACC1 gene. This alteration results from a A to G substitution at nucleotide position 38, causing the glutamine (Q) at amino acid position 13 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	Pathogenic	0.82
BayesDel_addAF	Uncertain	0.046	T
BayesDel_noAF	Benign	-0.17
CADD	Pathogenic	27
DANN	Uncertain	1.0
DEOGEN2	Benign	0.17	T;T;.
Eigen	Uncertain	0.58
Eigen_PC	Uncertain	0.54
FATHMM_MKL	Uncertain	0.92	D
LIST_S2	Uncertain	0.89	D;D;D
M_CAP	Uncertain	0.12	D
MetaRNN	Uncertain	0.46	T;T;T
MetaSVM	Uncertain	-0.27	T
MutationAssessor	Uncertain	2.6	.;M;M
PrimateAI	Pathogenic	0.85	D
PROVEAN	Uncertain	-3.4	D;N;N
REVEL	Benign	0.20
Sift	Pathogenic	0.0	D;D;D
Sift4G	Pathogenic	0.0	D;D;T
Polyphen		0.98	.;D;D
Vest4		0.63, 0.28
MutPred		0.52		Gain of MoRF binding (P = 0.0946);Gain of MoRF binding (P = 0.0946);Gain of MoRF binding (P = 0.0946);
MVP		0.67
MPC		0.52
ClinPred		0.98	D
GERP RS		4.8
Varity_R		0.27
gMVP		0.33

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: rs952240000; hg19: chr8-38645138;