chr8-94935974-A-G

Variant names:

• chr8-94935974-A-G
• rs10956932
• NM_033285.4:c.473+3886T>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.473+3886T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.628 in 152,026 control chromosomes in the GnomAD database, including 30,561 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 0.63 (30561 hom., cov: 31)
• Consequence: TP53INP1 NM_033285.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.334
• 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=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.768 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TP53INP1	NM_033285.4	c.473+3886T>C		intron_variant	Intron 3 of 3	ENST00000342697.5	NP_150601.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TP53INP1	ENST00000342697.5	c.473+3886T>C		intron_variant	Intron 3 of 3	1	NM_033285.4	ENSP00000344215.4

Frequencies

GnomAD3 genomes AF: 0.628 AC: 95348 AN: 151908 Hom.: 30532 Cov.: 31

Gnomad AFR AF: 0.508

Gnomad AMI AF: 0.677

Gnomad AMR AF: 0.620

Gnomad ASJ AF: 0.607

Gnomad EAS AF: 0.788

Gnomad SAS AF: 0.723

Gnomad FIN AF: 0.742

Gnomad MID AF: 0.690

Gnomad NFE AF: 0.665

Gnomad OTH AF: 0.644

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

GnomAD4 genome AF: 0.628 AC: 95424 AN: 152026 Hom.: 30561 Cov.: 31 AF XY: 0.634 AC XY: 47153 AN XY: 74324

African (AFR) AF: 0.508 AC: 21073 AN: 41442

American (AMR) AF: 0.620 AC: 9487 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.607 AC: 2099 AN: 3460

East Asian (EAS) AF: 0.788 AC: 4067 AN: 5162

South Asian (SAS) AF: 0.724 AC: 3491 AN: 4824

European-Finnish (FIN) AF: 0.742 AC: 7844 AN: 10570

Middle Eastern (MID) AF: 0.711 AC: 209 AN: 294

European-Non Finnish (NFE) AF: 0.665 AC: 45183 AN: 67960

Other (OTH) AF: 0.642 AC: 1354 AN: 2108

Alfa AF: 0.660 Hom.: 18505

Bravo AF: 0.615

Asia WGS AF: 0.684 AC: 2380 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.3
DANN	Benign	0.61
PhyloP100		-0.33
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: rs10956932; hg19: chr8-95948202;