chr8-94948283-T-C

Variant names:

• chr8-94948283-T-C
• rs896854
• NM_033285.4:c.-151+871A>G

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+871A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.461 in 152,062 control chromosomes in the GnomAD database, including 17,112 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 0.46 (17112 hom., cov: 32)
• Consequence: TP53INP1 NM_033285.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.287
• Publications: 177 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 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=-0.84).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.704 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TP53INP1	NM_033285.4	MANE Select	c.-151+871A>G		intron	N/A	NP_150601.1
	NDUFAF6	NM_001354516.2		c.-263-9712T>C		intron	N/A	NP_001341445.1
	NDUFAF6	NM_001354514.2		c.-485-9712T>C		intron	N/A	NP_001341443.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TP53INP1	ENST00000342697.5	TSL:1 MANE Select	c.-151+871A>G		intron	N/A	ENSP00000344215.4
	TP53INP1	ENST00000448464.6	TSL:1	c.-151+871A>G		intron	N/A	ENSP00000390063.2
	NDUFAF6	ENST00000396113.5	TSL:5	c.-799+2664T>C		intron	N/A	ENSP00000379419.1

Frequencies

GnomAD3 genomes AF: 0.461 AC: 70004 AN: 151944 Hom.: 17108 Cov.: 32

Gnomad AFR AF: 0.301

Gnomad AMI AF: 0.544

Gnomad AMR AF: 0.494

Gnomad ASJ AF: 0.551

Gnomad EAS AF: 0.724

Gnomad SAS AF: 0.595

Gnomad FIN AF: 0.533

Gnomad MID AF: 0.456

Gnomad NFE AF: 0.503

Gnomad OTH AF: 0.490

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

GnomAD4 genome AF: 0.461 AC: 70047 AN: 152062 Hom.: 17112 Cov.: 32 AF XY: 0.467 AC XY: 34681 AN XY: 74320

African (AFR) AF: 0.301 AC: 12499 AN: 41480

American (AMR) AF: 0.495 AC: 7555 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.551 AC: 1913 AN: 3472

East Asian (EAS) AF: 0.723 AC: 3738 AN: 5168

South Asian (SAS) AF: 0.596 AC: 2874 AN: 4824

European-Finnish (FIN) AF: 0.533 AC: 5617 AN: 10530

Middle Eastern (MID) AF: 0.463 AC: 136 AN: 294

European-Non Finnish (NFE) AF: 0.503 AC: 34187 AN: 67998

Other (OTH) AF: 0.490 AC: 1034 AN: 2112

Alfa AF: 0.493 Hom.: 61944

Bravo AF: 0.454

Asia WGS AF: 0.593 AC: 2062 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	7.7
DANN	Benign	0.64
PhyloP100		-0.29
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: rs896854; hg19: chr8-95960511;