8-94947580-A-G

Variant names:

• chr8-94947580-A-G
• rs896855
• NM_033285.4:c.-151+1574T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_033285.4(TP53INP1):​c.-151+1574T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.438 in 152,046 control chromosomes in the GnomAD database, including 15,668 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 0.44 (15668 hom., cov: 33)
• Consequence: TP53INP1 NM_033285.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0260
• Publications: 7 publications found

Genes affected

TP53INP1 (HGNC:18022): (tumor protein p53 inducible nuclear protein 1) Predicted to enable antioxidant activity. Involved in autophagic cell death; positive regulation of autophagy; and positive regulation of transcription, DNA-templated. Located in autophagosome; cytosol; and nucleus. [provided by Alliance of Genome Resources, Apr 2022]

NDUFAF6 (HGNC:28625): (NADH:ubiquinone oxidoreductase complex assembly factor 6) This gene encodes a protein that localizes to mitochondria and contains a predicted phytoene synthase domain. The encoded protein plays an important role in the assembly of complex I (NADH-ubiquinone oxidoreductase) of the mitochondrial respiratory chain through regulation of subunit ND1 biogenesis. Mutations in this gene are associated with complex I enzymatic deficiency. [provided by RefSeq, Nov 2011]

NDUFAF6 Gene-Disease associations (from GenCC):

• Leigh syndrome

  Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
• mitochondrial disease

  Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
• mitochondrial complex I deficiency, nuclear type 17

  Inheritance: AR Classification: MODERATE Submitted by: Ambry Genetics
• primary Fanconi syndrome

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• Leigh syndrome with leukodystrophy

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
• Fanconi renotubular syndrome 5

  Inheritance: AR Classification: LIMITED Submitted by: Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.7).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.698 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_033285.4. 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
	TP53INP1	NM_033285.4	MANE Select	c.-151+1574T>C		intron	N/A	NP_150601.1	Q96A56-1
	NDUFAF6	NM_001354516.2		c.-263-10415A>G		intron	N/A	NP_001341445.1	Q330K2-2
	NDUFAF6	NM_001354514.2		c.-485-10415A>G		intron	N/A	NP_001341443.1	A0A075B6P0

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TP53INP1	ENST00000342697.5	TSL:1 MANE Select	c.-151+1574T>C		intron	N/A	ENSP00000344215.4	Q96A56-1
	TP53INP1	ENST00000448464.6	TSL:1	c.-151+1574T>C		intron	N/A	ENSP00000390063.2	Q96A56-2
	NDUFAF6	ENST00000396113.5	TSL:5	c.-799+1961A>G		intron	N/A	ENSP00000379419.1	A0A075B6P0

Frequencies

GnomAD3 genomes AF: 0.438 AC: 66546 AN: 151928 Hom.: 15663 Cov.: 33

Gnomad AFR AF: 0.268

Gnomad AMI AF: 0.545

Gnomad AMR AF: 0.473

Gnomad ASJ AF: 0.467

Gnomad EAS AF: 0.718

Gnomad SAS AF: 0.573

Gnomad FIN AF: 0.530

Gnomad MID AF: 0.434

Gnomad NFE AF: 0.485

Gnomad OTH AF: 0.467

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

GnomAD4 genome AF: 0.438 AC: 66589 AN: 152046 Hom.: 15668 Cov.: 33 AF XY: 0.445 AC XY: 33071 AN XY: 74310

African (AFR) AF: 0.268 AC: 11108 AN: 41490

American (AMR) AF: 0.474 AC: 7239 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.467 AC: 1620 AN: 3468

East Asian (EAS) AF: 0.717 AC: 3696 AN: 5154

South Asian (SAS) AF: 0.574 AC: 2767 AN: 4820

European-Finnish (FIN) AF: 0.530 AC: 5582 AN: 10536

Middle Eastern (MID) AF: 0.439 AC: 129 AN: 294

European-Non Finnish (NFE) AF: 0.485 AC: 32968 AN: 67994

Other (OTH) AF: 0.467 AC: 984 AN: 2108

Alfa AF: 0.446 Hom.: 2059

Bravo AF: 0.430

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.70
CADD	Benign	10
DANN	Benign	0.87
PhyloP100		0.026
Mutation Taster		=100/0	polymorphism (auto)

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: rs896855; hg19: chr8-95959808;