4-1722852-C-T

Variant names:

• chr4-1722852-C-T
• rs1374468
• NM_006342.3:c.-1-569C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_006342.3(TACC3):​c.-1-569C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.181 in 152,130 control chromosomes in the GnomAD database, including 2,747 homozygotes. 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: 𝑓 0.18 (2747 hom., cov: 32)
• Consequence: TACC3 NM_006342.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.687
• Publications: 13 publications found

Genes affected

TACC3 (HGNC:11524): (transforming acidic coiled-coil containing protein 3) This gene encodes a member of the transforming acidic colied-coil protein family. The encoded protein is a motor spindle protein that may play a role in stabilization of the mitotic spindle. This protein may also play a role in growth a differentiation of certain cancer cells. [provided by RefSeq, Nov 2011]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.2 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006342.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TACC3	NM_006342.3	MANE Select	c.-1-569C>T		intron	N/A	NP_006333.1
	TACC3	NM_001441304.1		c.-1-569C>T		intron	N/A	NP_001428233.1
	TACC3	NM_001441305.1		c.-1-569C>T		intron	N/A	NP_001428234.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TACC3	ENST00000313288.9	TSL:1 MANE Select	c.-1-569C>T		intron	N/A	ENSP00000326550.4
	TACC3	ENST00000651472.1		c.-1-569C>T		intron	N/A	ENSP00000498361.1
	TACC3	ENST00000652770.1		c.-2+459C>T		intron	N/A	ENSP00000498219.1

Frequencies

GnomAD3 genomes AF: 0.181 AC: 27526 AN: 152014 Hom.: 2735 Cov.: 32

Gnomad AFR AF: 0.203

Gnomad AMI AF: 0.315

Gnomad AMR AF: 0.152

Gnomad ASJ AF: 0.237

Gnomad EAS AF: 0.0139

Gnomad SAS AF: 0.161

Gnomad FIN AF: 0.0860

Gnomad MID AF: 0.161

Gnomad NFE AF: 0.199

Gnomad OTH AF: 0.180

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.181 AC: 27574 AN: 152130 Hom.: 2747 Cov.: 32 AF XY: 0.176 AC XY: 13093 AN XY: 74388

African (AFR) AF: 0.204 AC: 8439 AN: 41468

American (AMR) AF: 0.152 AC: 2325 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.237 AC: 822 AN: 3468

East Asian (EAS) AF: 0.0139 AC: 72 AN: 5180

South Asian (SAS) AF: 0.161 AC: 774 AN: 4820

European-Finnish (FIN) AF: 0.0860 AC: 912 AN: 10608

Middle Eastern (MID) AF: 0.167 AC: 49 AN: 294

European-Non Finnish (NFE) AF: 0.199 AC: 13512 AN: 67990

Other (OTH) AF: 0.181 AC: 382 AN: 2110

Alfa AF: 0.191 Hom.: 9919

Bravo AF: 0.186

Asia WGS AF: 0.0980 AC: 339 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	2.6
DANN	Benign	0.45
PhyloP100		-0.69
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs1374468; hg19: chr4-1724579;