rs1713669

Positions:

• chr8-94946409-C-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_033285.4(TP53INP1):​c.-151+2745G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.337 in 151,656 control chromosomes in the GnomAD database, including 9,365 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 0.34 (9365 hom., cov: 28)
• Consequence: TP53INP1 NM_033285.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.362

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=-0.83).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.406 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TP53INP1	NM_033285.4	c.-151+2745G>C		intron_variant		ENST00000342697.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TP53INP1	ENST00000342697.5	c.-151+2745G>C		intron_variant		1	NM_033285.4	P1

Frequencies

GnomAD3 genomes AF: 0.338 AC: 51173 AN: 151538 Hom.: 9369 Cov.: 28

Gnomad AFR AF: 0.204

Gnomad AMI AF: 0.441

Gnomad AMR AF: 0.385

Gnomad ASJ AF: 0.372

Gnomad EAS AF: 0.166

Gnomad SAS AF: 0.321

Gnomad FIN AF: 0.400

Gnomad MID AF: 0.402

Gnomad NFE AF: 0.410

Gnomad OTH AF: 0.329

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

GnomAD4 genome AF: 0.337 AC: 51176 AN: 151656 Hom.: 9365 Cov.: 28 AF XY: 0.337 AC XY: 24928 AN XY: 74068

Gnomad4 AFR AF: 0.204

Gnomad4 AMR AF: 0.385

Gnomad4 ASJ AF: 0.372

Gnomad4 EAS AF: 0.166

Gnomad4 SAS AF: 0.321

Gnomad4 FIN AF: 0.400

Gnomad4 NFE AF: 0.410

Gnomad4 OTH AF: 0.326

Alfa AF: 0.373 Hom.: 1376

Bravo AF: 0.328

Asia WGS AF: 0.262 AC: 911 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	2.0
DANN	Benign	0.50

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: rs1713669; hg19: chr8-95958637;