6-13615381-C-T

Variant names:

• chr6-13615381-C-T
• rs767023705
• NM_016167.5:c.23C>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_016167.5(NOL7):​c.23C>T​(p.Ala8Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000659 in 1,365,724 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A8E) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000066 (0 hom.)
• Consequence: NOL7 NM_016167.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.33
• Publications: 0 publications found

Genes affected

NOL7 (HGNC:21040): (nucleolar protein 7) The protein encoded by this gene localizes to the nucleolus, where it maintains nucleolar structure and cell growth rates. The encoded protein also functions as a tumor suppressor and regulator of angiogenesis. The RB tumor suppressor gene recruits transcription factors to this gene and positively regulates its expression. Two transcript variants encoding the same protein have been found for this gene. [provided by RefSeq, Dec 2015]

SIRT5 (HGNC:14933): (sirtuin 5) This gene encodes a member of the sirtuin family of proteins, homologs to the yeast Sir2 protein. Members of the sirtuin family are characterized by a sirtuin core domain and grouped into four classes. The functions of human sirtuins have not yet been determined; however, yeast sirtuin proteins are known to regulate epigenetic gene silencing and suppress recombination of rDNA. Studies suggest that the human sirtuins may function as intracellular regulatory proteins with mono-ADP-ribosyltransferase activity. The protein encoded by this gene is included in class III of the sirtuin family. Alternative splicing of this gene results in multiple transcript variants. [provided by RefSeq, Jul 2010]

ENSG00000261071 (HGNC:):

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.035557628).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_016167.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NOL7	NM_016167.5	MANE Select	c.23C>T	p.Ala8Val	missense	Exon 1 of 8	NP_057251.2
	NOL7	NM_001317724.2		c.23C>T	p.Ala8Val	missense	Exon 1 of 9	NP_001304653.1	Q9UMY1-1
	SIRT5	NM_012241.5	MANE Select	c.*3516C>T		downstream_gene	N/A	NP_036373.1	Q9NXA8-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NOL7	ENST00000451315.7	TSL:1 MANE Select	c.23C>T	p.Ala8Val	missense	Exon 1 of 8	ENSP00000405674.2	Q9UMY1-1
	NOL7	ENST00000865196.1		c.23C>T	p.Ala8Val	missense	Exon 1 of 9	ENSP00000535255.1
	NOL7	ENST00000865197.1		c.23C>T	p.Ala8Val	missense	Exon 1 of 6	ENSP00000535256.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000659 AC: 9 AN: 1365724 Hom.: 0 Cov.: 31 AF XY: 0.00000447 AC XY: 3 AN XY: 671328

African (AFR) AF: 0.00 AC: 0 AN: 30754

American (AMR) AF: 0.00 AC: 0 AN: 31652

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 22498

East Asian (EAS) AF: 0.00 AC: 0 AN: 35598

South Asian (SAS) AF: 0.00 AC: 0 AN: 73266

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 44332

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4058

European-Non Finnish (NFE) AF: 0.00000844 AC: 9 AN: 1066966

Other (OTH) AF: 0.00 AC: 0 AN: 56600

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.10
BayesDel_addAF	Benign	-0.28	T
BayesDel_noAF	Benign	-0.64
CADD	Benign	19
DANN	Uncertain	1.0
DEOGEN2	Benign	0.017	T
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.0
FATHMM_MKL	Benign	0.19	N
LIST_S2	Benign	0.64	T
M_CAP	Benign	0.020	T
MetaRNN	Benign	0.036	T
MetaSVM	Benign	-0.94	T
MutationAssessor	Benign	0.55	N
PhyloP100		1.3
PrimateAI	Uncertain	0.73	T
PROVEAN	Benign	-0.75	N
REVEL	Benign	0.088
Sift	Benign	0.50	T
Sift4G	Benign	0.65	T
Polyphen		0.0010	B
Vest4		0.095
MutPred		0.12		Loss of glycosylation at P6 (P = 0.0617)
MVP		0.072
MPC		0.86
ClinPred		0.087	T
GERP RS		-0.40
PromoterAI		-0.049	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.036
gMVP		0.11
Mutation Taster		=98/2	polymorphism

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

Other links and lift over

dbSNP: rs767023705; hg19: chr6-13615613;