chr9-85959866-T-G

Position:

• chr9-85959866-T-G

Variant summary

Our verdict is Benign. Variant got -7 ACMG points: 1P and 8B. PP2 BP4_Moderate BP6_Moderate BS2

The NM_024635.4(NAA35):​c.347T>G​(p.Leu116Trp) variant causes a missense, splice region change. The variant allele was found at a frequency of 0.00156 in 1,604,960 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 2/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0010 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0016 (1 hom.)
• Consequence: NAA35 NM_024635.4 missense, splice_region
• Scores: Splicing: ADA: 0.8280
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 6.77

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]

ACMG classification

Verdict is Benign. Variant got -7 ACMG points.

• PP2: Missense variant where missense usually causes diseases, NAA35
• BP4: Computational evidence support a benign effect (MetaRNN=0.14001492).
• BP6: Variant 9-85959866-T-G is Benign according to our data. Variant chr9-85959866-T-G is described in ClinVar as [Likely_benign]. Clinvar id is 2047181.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High AC in GnomAd4 at 159 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NAA35	NM_024635.4	c.347T>G	p.Leu116Trp	missense_variant, splice_region_variant	5/23	ENST00000361671.10
NAA35	NM_001321881.2	c.347T>G	p.Leu116Trp	missense_variant, splice_region_variant	5/23
NAA35	NM_001321882.2	c.347T>G	p.Leu116Trp	missense_variant, splice_region_variant	5/23
NAA35	XM_005252127.5	c.347T>G	p.Leu116Trp	missense_variant, splice_region_variant	5/23

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NAA35	ENST00000361671.10	c.347T>G	p.Leu116Trp	missense_variant, splice_region_variant	5/23	1	NM_024635.4	P1
NAA35	ENST00000376040.2	c.347T>G	p.Leu116Trp	missense_variant, splice_region_variant	5/12	2
NAA35	ENST00000416045.4	n.444T>G		splice_region_variant, non_coding_transcript_exon_variant	5/7	3

Frequencies

GnomAD3 genomes AF: 0.00104 AC: 159 AN: 152226 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000362

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000654

Gnomad ASJ AF: 0.000288

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000282

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00203

Gnomad OTH AF: 0.000479

GnomAD3 exomes AF: 0.000996 AC: 246 AN: 246898 Hom.: 0 AF XY: 0.00101 AC XY: 135 AN XY: 133448

Gnomad AFR exome AF: 0.000247

Gnomad AMR exome AF: 0.0000604

Gnomad ASJ exome AF: 0.000101

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.0000465

Gnomad NFE exome AF: 0.00210

Gnomad OTH exome AF: 0.000166

GnomAD4 exome AF: 0.00161 AC: 2344 AN: 1452616 Hom.: 1 Cov.: 28 AF XY: 0.00157 AC XY: 1132 AN XY: 722952

Gnomad4 AFR exome AF: 0.000211

Gnomad4 AMR exome AF: 0.0000461

Gnomad4 ASJ exome AF: 0.0000770

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.000300

Gnomad4 NFE exome AF: 0.00204

Gnomad4 OTH exome AF: 0.00102

GnomAD4 genome AF: 0.00104 AC: 159 AN: 152344 Hom.: 0 Cov.: 32 AF XY: 0.000980 AC XY: 73 AN XY: 74498

Gnomad4 AFR AF: 0.000361

Gnomad4 AMR AF: 0.0000653

Gnomad4 ASJ AF: 0.000288

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.000282

Gnomad4 NFE AF: 0.00203

Gnomad4 OTH AF: 0.000474

Alfa AF: 0.00255 Hom.: 0

Bravo AF: 0.000929

TwinsUK AF: 0.00135 AC: 5

ALSPAC AF: 0.00156 AC: 6

ESP6500AA AF: 0.000227 AC: 1

ESP6500EA AF: 0.00198 AC: 17

ExAC AF: 0.00120 AC: 146

Asia WGS AF: 0.000289 AC: 1 AN: 3470

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Invitae

Jan 09, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.84
BayesDel_addAF	Uncertain	0.12	D
BayesDel_noAF	Pathogenic	0.39
CADD	Pathogenic	31
DANN	Benign	0.96
DEOGEN2	Benign	0.33	T;.
Eigen	Uncertain	0.66
Eigen_PC	Pathogenic	0.67
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.91	D;D
M_CAP	Benign	0.013	T
MetaRNN	Benign	0.14	T;T
MetaSVM	Benign	-0.51	T
MutationAssessor	Uncertain	2.1	M;M
MutationTaster	Benign	1.0	D;D
PrimateAI	Pathogenic	0.88	D
PROVEAN	Uncertain	-3.9	D;D
REVEL	Uncertain	0.47
Sift	Uncertain	0.0020	D;D
Sift4G	Uncertain	0.0040	D;D
Polyphen		1.0	D;.
Vest4		0.89
MVP		0.26
MPC		2.4
ClinPred		0.14	T
GERP RS		5.5
Varity_R		0.59
gMVP		0.85

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.83
dbscSNV1_RF	Pathogenic	0.78
SpliceAI score (max)		0.010		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

Other links and lift over

dbSNP: rs41283649; hg19: chr9-88574781;