Variant 6-30642848-C-T details in Genebe, Genetics Data Aggregator

Variant summary

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

The ENST00000330083.6(ATAT1):c.769C>T(p.Arg257Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000201 in 1,591,812 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 (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R257G) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.000020 ( 0 hom., cov: 26)

Exomes 𝑓: 0.000020 ( 0 hom. )

Consequence

ATAT1
ENST00000330083.6 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.61

Variant links:

Genes affected

ATAT1 (HGNC:21186): (alpha tubulin acetyltransferase 1) This gene encodes a protein that localizes to clathrin-coated pits, where it acetylates alpha tubulin on lysine 40. This process may be important in microtubule growth, for instance during chemotaxis and the formation of cilium. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jan 2016]

ATAT1 links:

ATAT1 (HGNC:):

ATAT1 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=0.24194819).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ATAT1	NM_001031722.4 linkuse as main transcript	c.769C>T	p.Arg257Cys	missense_variant	10/13	ENST00000330083.6	NP_001026892.1	Q5SQI0-2A0A1U9X797

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ATAT1	ENST00000330083.6 linkuse as main transcript	c.769C>T	p.Arg257Cys	missense_variant	10/13	1	NM_001031722.4	ENSP00000327832.5		Q5SQI0-2
ATAT1	ENST00000376485.9 linkuse as main transcript	c.805C>T	p.Arg269Cys	missense_variant	10/13	5		ENSP00000365668.4		Q5SQI0-1

Frequencies

GnomAD3 genomes

AF:

0.0000203

AC:

AN:

147718

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000251

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000202

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000149

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000221

AC:

AN:

226076

Hom.:

AF XY:

0.00000809

AC XY:

AN XY:

123546

show subpopulations

Gnomad AFR exome

AF:

0.000147

Gnomad AMR exome

AF:

0.0000303

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:

0.0000203

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000201

AC:

AN:

1444094

Hom.:

Cov.:

AF XY:

0.0000153

AC XY:

AN XY:

717744

show subpopulations

Gnomad4 AFR exome

AF:

0.0000303

Gnomad4 AMR exome

AF:

0.0000458

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000118

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000209

Gnomad4 OTH exome

AF:

0.0000337

GnomAD4 genome

AF:

0.0000203

AC:

AN:

147718

Hom.:

Cov.:

AF XY:

0.0000139

AC XY:

AN XY:

71752

show subpopulations

Gnomad4 AFR

AF:

0.0000251

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000202

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000149

Gnomad4 OTH

AF:

0.00

ExAC

AF:

0.0000165

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

Aug 16, 2022

The c.769C>T (p.R257C) alteration is located in exon 10 (coding exon 10) of the ATAT1 gene. This alteration results from a C to T substitution at nucleotide position 769, causing the arginine (R) at amino acid position 257 to be replaced by a cysteine (C). 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

0.33

BayesDel_addAF

Uncertain

0.15

BayesDel_noAF

Uncertain

-0.020

CADD

Pathogenic

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.049

.;T;.;.;.;.

Eigen

Uncertain

0.57

Eigen_PC

Uncertain

0.54

FATHMM_MKL

Uncertain

0.81

M_CAP

Benign

0.024

MetaRNN

Benign

0.24

T;T;T;T;T;T

MetaSVM

Benign

-0.38

MutationAssessor

Benign

0.90

.;L;.;L;L;.

MutationTaster

Benign

1.0

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

PrimateAI

Pathogenic

0.84

PROVEAN

Benign

-0.16

N;N;N;N;N;N

REVEL

Benign

0.14

Sift

Uncertain

0.0010

D;D;D;D;D;D

Sift4G

Uncertain

0.0060

D;D;D;D;D;D

Polyphen

1.0, 1.0

.;D;D;.;D;D

Vest4

0.47

MutPred

0.32

.;Gain of catalytic residue at P268 (P = 0.0233);.;Gain of catalytic residue at P268 (P = 0.0233);Gain of catalytic residue at P268 (P = 0.0233);.;

MVP

0.44

MPC

1.5

ClinPred

0.77

GERP RS

4.9

Varity_R

0.13

gMVP

0.42

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