9-136063400-C-T

Position:

• chr9-136063400-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_144653.5(NACC2):​c.-59-12820G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.746 in 152,098 control chromosomes in the GnomAD database, including 43,206 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.75 (43206 hom., cov: 32)
• Consequence: NACC2 NM_144653.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.47

Genes affected

NACC2 (HGNC:23846): (NACC family member 2) Enables several functions, including DNA-binding transcription repressor activity, RNA polymerase II-specific; histone deacetylase binding activity; and protein homodimerization activity. Involved in several processes, including negative regulation of G1/S transition of mitotic cell cycle by negative regulation of transcription from RNA polymerase II promoter; positive regulation of intrinsic apoptotic signaling pathway in response to DNA damage; and protein homooligomerization. Located in chromatin; mitochondrion; and nucleolus. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.02).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.827 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NACC2	NM_144653.5	c.-59-12820G>A		intron_variant		ENST00000277554.4	NP_653254.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NACC2	ENST00000277554.4	c.-59-12820G>A		intron_variant		1	NM_144653.5	ENSP00000277554.2

Frequencies

GnomAD3 genomes AF: 0.746 AC: 113336 AN: 151980 Hom.: 43177 Cov.: 32

Gnomad AFR AF: 0.589

Gnomad AMI AF: 0.817

Gnomad AMR AF: 0.774

Gnomad ASJ AF: 0.860

Gnomad EAS AF: 0.569

Gnomad SAS AF: 0.787

Gnomad FIN AF: 0.783

Gnomad MID AF: 0.756

Gnomad NFE AF: 0.832

Gnomad OTH AF: 0.755

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.746 AC: 113415 AN: 152098 Hom.: 43206 Cov.: 32 AF XY: 0.744 AC XY: 55276 AN XY: 74342

Gnomad4 AFR AF: 0.589

Gnomad4 AMR AF: 0.774

Gnomad4 ASJ AF: 0.860

Gnomad4 EAS AF: 0.569

Gnomad4 SAS AF: 0.788

Gnomad4 FIN AF: 0.783

Gnomad4 NFE AF: 0.832

Gnomad4 OTH AF: 0.758

Alfa AF: 0.815 Hom.: 66209

Bravo AF: 0.736

Asia WGS AF: 0.727 AC: 2533 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.022
DANN	Benign	0.33

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs871095; hg19: chr9-138955246;