8-94926194-C-A

Variant names:

• chr8-94926194-C-A
• rs7760
• NM_033285.4:c.*4285G>T

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_033285.4(TP53INP1):​c.*4285G>T variant causes a 3 prime UTR change. The variant allele was found at a frequency of 0.817 in 152,494 control chromosomes in the GnomAD database, including 51,928 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 0.82 (51749 hom., cov: 31)
  • Exomes 𝑓: 0.91 (179 hom.)
• Consequence: TP53INP1 NM_033285.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.64
• Publications: 11 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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.36).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.879 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TP53INP1	NM_033285.4	c.*4285G>T		3_prime_UTR_variant	Exon 4 of 4	ENST00000342697.5	NP_150601.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TP53INP1	ENST00000342697.5	c.*4285G>T		3_prime_UTR_variant	Exon 4 of 4	1	NM_033285.4	ENSP00000344215.4

Frequencies

GnomAD3 genomes AF: 0.817 AC: 124175 AN: 151946 Hom.: 51717 Cov.: 31

Gnomad AFR AF: 0.636

Gnomad AMI AF: 0.891

Gnomad AMR AF: 0.875

Gnomad ASJ AF: 0.828

Gnomad EAS AF: 0.897

Gnomad SAS AF: 0.890

Gnomad FIN AF: 0.923

Gnomad MID AF: 0.829

Gnomad NFE AF: 0.885

Gnomad OTH AF: 0.822

GnomAD4 exome AF: 0.909 AC: 391 AN: 430 Hom.: 179 Cov.: 0 AF XY: 0.915 AC XY: 236 AN XY: 258

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 0.910 AC: 386 AN: 424

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 1.00 AC: 2 AN: 2

Other (OTH) AF: 0.750 AC: 3 AN: 4

GnomAD4 genome AF: 0.817 AC: 124257 AN: 152064 Hom.: 51749 Cov.: 31 AF XY: 0.821 AC XY: 61050 AN XY: 74334

African (AFR) AF: 0.636 AC: 26319 AN: 41386

American (AMR) AF: 0.875 AC: 13390 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.828 AC: 2874 AN: 3472

East Asian (EAS) AF: 0.897 AC: 4643 AN: 5176

South Asian (SAS) AF: 0.891 AC: 4289 AN: 4814

European-Finnish (FIN) AF: 0.923 AC: 9769 AN: 10588

Middle Eastern (MID) AF: 0.823 AC: 242 AN: 294

European-Non Finnish (NFE) AF: 0.885 AC: 60187 AN: 68008

Other (OTH) AF: 0.819 AC: 1731 AN: 2114

Alfa AF: 0.870 Hom.: 74358

Bravo AF: 0.805

Asia WGS AF: 0.861 AC: 2993 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.36
CADD	Benign	14
DANN	Benign	0.87
PhyloP100		3.6
Mutation Taster		=97/3	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: rs7760; hg19: chr8-95938422;