chr9-85962005-C-G

Position:

• chr9-85962005-C-G

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2 BP4_Strong BP6_Moderate

The NM_024635.4(NAA35):​c.349-8C>G variant causes a splice region, splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 31)
• Consequence: NAA35 NM_024635.4 splice_region, splice_polypyrimidine_tract, intron
• Scores: Splicing: ADA: 0.00009974
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.421

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 Likely_benign. Variant got -4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.74).
• BP6: Variant 9-85962005-C-G is Benign according to our data. Variant chr9-85962005-C-G is described in ClinVar as [Likely_benign]. Clinvar id is 2122822.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NAA35	NM_024635.4	c.349-8C>G		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		ENST00000361671.10
NAA35	NM_001321881.2	c.349-8C>G		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant
NAA35	NM_001321882.2	c.349-8C>G		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant
NAA35	XM_005252127.5	c.349-8C>G		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NAA35	ENST00000361671.10	c.349-8C>G		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		1	NM_024635.4	P1
NAA35	ENST00000376040.2	c.349-8C>G		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		2
NAA35	ENST00000416045.4	n.446-8C>G		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 29

GnomAD4 genome Cov.: 31

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

Aug 11, 2022

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.74
CADD	Benign	8.6
DANN	Benign	0.60
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		2.2

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.00010
dbscSNV1_RF	Benign	0.0080
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

No publications associated with this variant yet.

Other links and lift over

hg19: chr9-88576920;