chr9-85942240-A-C

Position:

• chr9-85942240-A-C

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_Strong BP6_Moderate BP7 BS2

The NM_024635.4(NAA35):​c.81A>C​(p.Thr27=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000547 in 1,461,834 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 Likely benign (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000055 (0 hom.)
• Consequence: NAA35 NM_024635.4 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.113

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 -11 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.68).
• BP6: Variant 9-85942240-A-C is Benign according to our data. Variant chr9-85942240-A-C is described in ClinVar as [Likely_benign]. Clinvar id is 2040321.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-0.113 with no splicing effect.
• BS2: High AC in GnomAdExome4 at 8 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NAA35	NM_024635.4	c.81A>C	p.Thr27=	synonymous_variant	2/23	ENST00000361671.10
NAA35	NM_001321881.2	c.81A>C	p.Thr27=	synonymous_variant	2/23
NAA35	NM_001321882.2	c.81A>C	p.Thr27=	synonymous_variant	2/23
NAA35	XM_005252127.5	c.81A>C	p.Thr27=	synonymous_variant	2/23

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NAA35	ENST00000361671.10	c.81A>C	p.Thr27=	synonymous_variant	2/23	1	NM_024635.4	P1
NAA35	ENST00000376040.2	c.81A>C	p.Thr27=	synonymous_variant	2/12	2
NAA35	ENST00000416045.4	n.178A>C		non_coding_transcript_exon_variant	2/7	3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000547 AC: 8 AN: 1461834 Hom.: 0 Cov.: 30 AF XY: 0.00000413 AC XY: 3 AN XY: 727216

Gnomad4 AFR exome AF: 0.000149

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.0000497

GnomAD4 genome Cov.: 33

Bravo AF: 0.00000378

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

Nov 27, 2023

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.68
CADD	Benign	9.0
DANN	Benign	0.63
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7

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

Other links and lift over

dbSNP: rs1828554842; hg19: chr9-88557155;