Variant 9-85962009-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_024635.4(NAA35):c.349-4A>G variant causes a splice region, splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000692 in 1,597,940 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00048 ( 0 hom., cov: 31)

Exomes 𝑓: 0.00071 ( 2 hom. )

Consequence

NAA35
NM_024635.4 splice_region, splice_polypyrimidine_tract, intron

Scores

Splicing: ADA: 0.0001136

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.984

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 -10 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.73).

BP6

Variant 9-85962009-A-G is Benign according to our data. Variant chr9-85962009-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 2052863.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High AC in GnomAd4 at 73 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	MANE
NAA35	NM_024635.4 linkuse as main transcript	c.349-4A>G	splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant	ENST00000361671.10
NAA35	NM_001321881.2 linkuse as main transcript	c.349-4A>G	splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant
NAA35	NM_001321882.2 linkuse as main transcript	c.349-4A>G	splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant
NAA35	XM_005252127.5 linkuse as main transcript	c.349-4A>G	splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Appris	UniProt
NAA35	ENST00000361671.10 linkuse as main transcript	c.349-4A>G	splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant	1	NM_024635.4	P1	Q5VZE5-1
NAA35	ENST00000376040.2 linkuse as main transcript	c.349-4A>G	splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant	2			Q5VZE5-2
NAA35	ENST00000416045.4 linkuse as main transcript	n.446-4A>G	splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant, non_coding_transcript_variant	3

Frequencies

GnomAD3 genomes

AF:

0.000481

AC:

AN:

151910

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000121

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000591

Gnomad ASJ

AF:

0.000288

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000838

Gnomad OTH

AF:

0.000479

GnomAD3 exomes

AF:

0.000439

AC:

104

AN:

236784

Hom.:

AF XY:

0.000344

AC XY:

AN XY:

128052

show subpopulations

Gnomad AFR exome

AF:

0.000250

Gnomad AMR exome

AF:

0.000228

Gnomad ASJ exome

AF:

0.000333

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0000943

Gnomad NFE exome

AF:

0.000787

Gnomad OTH exome

AF:

0.000353

GnomAD4 exome

AF:

0.000714

AC:

1032

AN:

1445912

Hom.:

Cov.:

AF XY:

0.000702

AC XY:

505

AN XY:

718898

show subpopulations

Gnomad4 AFR exome

AF:

0.000216

Gnomad4 AMR exome

AF:

0.000444

Gnomad4 ASJ exome

AF:

0.000239

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.0000377

Gnomad4 NFE exome

AF:

0.000866

Gnomad4 OTH exome

AF:

0.000671

GnomAD4 genome

AF:

0.000480

AC:

AN:

152028

Hom.:

Cov.:

AF XY:

0.000485

AC XY:

AN XY:

74296

show subpopulations

Gnomad4 AFR

AF:

0.000121

Gnomad4 AMR

AF:

0.000590

Gnomad4 ASJ

AF:

0.000288

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000838

Gnomad4 OTH

AF:

0.000474

Alfa

AF:

0.000595

Hom.:

Bravo

AF:

0.000465

EpiCase

AF:

0.000767

EpiControl

AF:

0.000653

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

Jun 29, 2023

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.73

CADD

Benign

4.0

DANN

Benign

0.59

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.00011

dbscSNV1_RF

Benign

0.028

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