Variant chr9-85958538-T-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 1P and 10B. PP2BP4_StrongBP6_ModerateBS2

The NM_024635.4(NAA35):c.225T>G(p.Ile75Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000186 in 1,611,804 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.000079 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00020 ( 2 hom. )

Consequence

NAA35
NM_024635.4 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.12

Variant links:

Genes affected

NAA35 (HGNC:24340): (N-alpha-acetyltransferase 35, NatC auxiliary subunit) Involved in negative regulation of apoptotic process. Located in cytosol; nucleoplasm; and plasma membrane. Part of NatC complex. Colocalizes with polysome. [provided by Alliance of Genome Resources, Apr 2022]

NAA35 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -9 ACMG points.

PP2

Missense variant where missense usually causes diseases, NAA35

BP4

Computational evidence support a benign effect (MetaRNN=0.016118914).

BP6

Variant 9-85958538-T-G is Benign according to our data. Variant chr9-85958538-T-G is described in ClinVar as [Likely_benign]. Clinvar id is 2919816.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High AC in GnomAd4 at 12 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
NAA35	NM_024635.4 linkuse as main transcript	c.225T>G	p.Ile75Met	missense_variant	4/23	ENST00000361671.10
NAA35	NM_001321881.2 linkuse as main transcript	c.225T>G	p.Ile75Met	missense_variant	4/23
NAA35	NM_001321882.2 linkuse as main transcript	c.225T>G	p.Ile75Met	missense_variant	4/23
NAA35	XM_005252127.5 linkuse as main transcript	c.225T>G	p.Ile75Met	missense_variant	4/23

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NAA35	ENST00000361671.10 linkuse as main transcript	c.225T>G	p.Ile75Met	missense_variant	4/23	1	NM_024635.4	P1	Q5VZE5-1
NAA35	ENST00000376040.2 linkuse as main transcript	c.225T>G	p.Ile75Met	missense_variant	4/12	2			Q5VZE5-2
NAA35	ENST00000416045.4 linkuse as main transcript	n.322T>G		non_coding_transcript_exon_variant	4/7	3

Frequencies

GnomAD3 genomes

AF:

0.0000788

AC:

AN:

152218

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:

0.00228

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000380

AC:

AN:

250016

Hom.:

AF XY:

0.000555

AC XY:

AN XY:

135174

show subpopulations

Gnomad AFR exome

AF:

0.0000618

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00306

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.000165

GnomAD4 exome

AF:

0.000197

AC:

288

AN:

1459468

Hom.:

Cov.:

AF XY:

0.000310

AC XY:

225

AN XY:

726064

show subpopulations

Gnomad4 AFR exome

AF:

0.0000299

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00320

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000270

Gnomad4 OTH exome

AF:

0.000149

GnomAD4 genome

AF:

0.0000788

AC:

AN:

152336

Hom.:

Cov.:

AF XY:

0.000107

AC XY:

AN XY:

74490

show subpopulations

Gnomad4 AFR

AF:

0.0000240

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00228

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000113

ExAC

AF:

0.000461

AC:

Asia WGS

AF:

0.00115

AC:

AN:

3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Invitae

Apr 14, 2023

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.20

BayesDel_addAF

Benign

-0.16

BayesDel_noAF

Uncertain

0.0

CADD

Benign

DANN

Benign

0.95

DEOGEN2

Benign

0.017

T;.

Eigen

Benign

-0.61

Eigen_PC

Benign

-0.44

FATHMM_MKL

Uncertain

0.88

LIST_S2

Uncertain

0.95

D;D

M_CAP

Benign

0.020

MetaRNN

Benign

0.016

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.075

N;N

MutationTaster

Benign

1.0

D;D

PrimateAI

Pathogenic

0.84

PROVEAN

Benign

0.26

N;N

REVEL

Benign

0.21

Sift

Benign

0.26

T;T

Sift4G

Benign

0.19

T;T

Polyphen

0.12

B;.

Vest4

0.69

MutPred

0.63

Gain of disorder (P = 0.0227);Gain of disorder (P = 0.0227);

MVP

0.46

MPC

0.87

ClinPred

0.043

GERP RS

0.66

Varity_R

0.091

gMVP

0.37

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