rs4735333

chr8-94942846-G-Achr8-94942846-G-C

Variant summary

Our verdict is Benign. Variant got -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

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=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.701 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TP53INP1	NM_033285.4	c.-150-1755C>T		intron_variant		ENST00000342697.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TP53INP1	ENST00000342697.5	c.-150-1755C>T		intron_variant		1	NM_033285.4	P1

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

Gnomad4 AFR AF: 0.269

Gnomad4 AMR AF: 0.474

Gnomad4 ASJ AF: 0.468

Gnomad4 EAS AF: 0.721

Gnomad4 SAS AF: 0.574

Gnomad4 FIN AF: 0.531

Gnomad4 NFE AF: 0.485

Gnomad4 OTH AF: 0.466

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 v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
Cadd	Benign	0.27
Dann	Benign	0.42

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: rs4735333; hg19: chr8-95955074;