rs10956932

chr8-94935974-A-Gchr8-94935974-A-T

Variant summary

Our verdict is Benign. Variant got -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

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]

ACMG classification

Verdict is Benign. Variant got -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/exons	MANE	UniProt
TP53INP1	NM_033285.4	c.473+3886T>C		intron_variant		ENST00000342697.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TP53INP1	ENST00000342697.5	c.473+3886T>C		intron_variant		1	NM_033285.4	P1

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

Gnomad4 AFR AF: 0.508

Gnomad4 AMR AF: 0.620

Gnomad4 ASJ AF: 0.607

Gnomad4 EAS AF: 0.788

Gnomad4 SAS AF: 0.724

Gnomad4 FIN AF: 0.742

Gnomad4 NFE AF: 0.665

Gnomad4 OTH AF: 0.642

Alfa AF: 0.660 Hom.: 16813

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

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

Publications

LitVar

Other links and lift over

dbSNP: rs10956932; hg19: chr8-95948202;