chr8-94942846-G-A

Variant names:

• chr8-94942846-G-A
• rs4735333
• NM_033285.4:c.-150-1755C>T

Variant summary

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

The NM_033285.4(TP53INP1):​c.-150-1755C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.439 in 152,004 control chromosomes in the GnomAD database, including 15,741 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 (15741 hom., cov: 31)
• Consequence: TP53INP1 NM_033285.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.682
• Publications: 10 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=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.701 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.-150-1755C>T		intron	N/A	NP_150601.1
	NDUFAF6	NM_001354516.2		c.-263-15149G>A		intron	N/A	NP_001341445.1
	NDUFAF6	NM_001354514.2		c.-485-15149G>A		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.-150-1755C>T		intron	N/A	ENSP00000344215.4
	TP53INP1	ENST00000448464.6	TSL:1	c.-150-1755C>T		intron	N/A	ENSP00000390063.2
	NDUFAF6	ENST00000396113.5	TSL:5	c.-935-2637G>A		intron	N/A	ENSP00000379419.1

Frequencies

GnomAD3 genomes AF: 0.439 AC: 66659 AN: 151886 Hom.: 15737 Cov.: 31

Gnomad AFR AF: 0.269

Gnomad AMI AF: 0.545

Gnomad AMR AF: 0.474

Gnomad ASJ AF: 0.468

Gnomad EAS AF: 0.722

Gnomad SAS AF: 0.573

Gnomad FIN AF: 0.531

Gnomad MID AF: 0.437

Gnomad NFE AF: 0.485

Gnomad OTH AF: 0.466

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

GnomAD4 genome AF: 0.439 AC: 66702 AN: 152004 Hom.: 15741 Cov.: 31 AF XY: 0.446 AC XY: 33133 AN XY: 74306

African (AFR) AF: 0.269 AC: 11164 AN: 41436

American (AMR) AF: 0.474 AC: 7245 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.468 AC: 1622 AN: 3468

East Asian (EAS) AF: 0.721 AC: 3718 AN: 5160

South Asian (SAS) AF: 0.574 AC: 2761 AN: 4812

European-Finnish (FIN) AF: 0.531 AC: 5607 AN: 10564

Middle Eastern (MID) AF: 0.442 AC: 130 AN: 294

European-Non Finnish (NFE) AF: 0.485 AC: 32976 AN: 67980

Other (OTH) AF: 0.466 AC: 983 AN: 2110

Alfa AF: 0.444 Hom.: 1925

Bravo AF: 0.431

Asia WGS AF: 0.571 AC: 1984 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.27
DANN	Benign	0.42
PhyloP100		-0.68
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: rs4735333; hg19: chr8-95955074;