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

Variant summary

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

The NM_001031722.4(ATAT1):c.769C>G(p.Arg257Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000804 in 1,591,904 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 0.00013 ( 0 hom., cov: 26)

Exomes 𝑓: 0.000075 ( 0 hom. )

Consequence

ATAT1
NM_001031722.4 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:

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=0.03914851).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ATAT1	NM_001413067.1 linkuse as main transcript	c.805C>G	p.Arg269Gly	missense_variant	10/13	ENST00000376485.9	NP_001399996.1
ATAT1	NR_033823.3 linkuse as main transcript	n.736+601C>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ATAT1	ENST00000376485.9 linkuse as main transcript	c.805C>G	p.Arg269Gly	missense_variant	10/13	5	NM_001413067.1	ENSP00000365668	A1	Q5SQI0-1

Frequencies

GnomAD3 genomes

AF:

0.000129

AC:

AN:

147718

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000503

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000203

Gnomad ASJ

AF:

0.00117

Gnomad EAS

AF:

0.000202

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.0000993

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000120

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000150

AC:

AN:

226076

Hom.:

AF XY:

0.000154

AC XY:

AN XY:

123546

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000909

Gnomad ASJ exome

AF:

0.00126

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000513

Gnomad NFE exome

AF:

0.0000608

Gnomad OTH exome

AF:

0.000534

GnomAD4 exome

AF:

0.0000755

AC:

109

AN:

1444094

Hom.:

Cov.:

AF XY:

0.0000780

AC XY:

AN XY:

717738

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000687

Gnomad4 ASJ exome

AF:

0.00112

Gnomad4 EAS exome

AF:

0.0000258

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.000618

Gnomad4 NFE exome

AF:

0.0000290

Gnomad4 OTH exome

AF:

0.000185

GnomAD4 genome

AF:

0.000129

AC:

AN:

147810

Hom.:

Cov.:

AF XY:

0.000139

AC XY:

AN XY:

71864

show subpopulations

Gnomad4 AFR

AF:

0.0000501

Gnomad4 AMR

AF:

0.000203

Gnomad4 ASJ

AF:

0.00117

Gnomad4 EAS

AF:

0.000203

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.0000993

Gnomad4 NFE

AF:

0.000120

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000218

Hom.:

Bravo

AF:

0.000102

ExAC

AF:

0.0000827

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

Mar 06, 2023

The c.769C>G (p.R257G) alteration is located in exon 10 (coding exon 10) of the ATAT1 gene. This alteration results from a C to G substitution at nucleotide position 769, causing the arginine (R) at amino acid position 257 to be replaced by a glycine (G). 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

Uncertain

0.45

BayesDel_addAF

Uncertain

0.11

BayesDel_noAF

Uncertain

-0.080

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Benign

0.041

.;T;.;.;.;.

Eigen

Uncertain

0.53

Eigen_PC

Uncertain

0.51

FATHMM_MKL

Uncertain

0.84

M_CAP

Benign

0.019

MetaRNN

Benign

0.039

T;T;T;T;T;T

MetaSVM

Benign

-0.41

MutationAssessor

Benign

0.90

.;L;.;L;L;.

MutationTaster

Benign

0.98

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

PrimateAI

Uncertain

0.79

PROVEAN

Benign

-1.4

N;N;N;N;N;N

REVEL

Benign

0.082

Sift

Uncertain

0.0030

D;D;D;D;D;D

Sift4G

Uncertain

0.049

D;D;D;T;T;D

Polyphen

0.93, 0.99, 1.0, 0.98

.;P;D;.;D;D

Vest4

0.33

MVP

0.45

MPC

1.3

ClinPred

0.089

GERP RS

4.9

Varity_R

0.24

gMVP

0.45

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