rs1713669

Variant names:

• chr8-94946409-C-G
• rs1713669
• NM_033285.4:c.-151+2745G>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.-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
• Publications: 8 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=-0.83).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.406 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_033285.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TP53INP1	NM_033285.4	MANE Select	c.-151+2745G>C		intron	N/A	NP_150601.1
	NDUFAF6	NM_001354516.2		c.-263-11586C>G		intron	N/A	NP_001341445.1
	NDUFAF6	NM_001354514.2		c.-485-11586C>G		intron	N/A	NP_001341443.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TP53INP1	ENST00000342697.5	TSL:1 MANE Select	c.-151+2745G>C		intron	N/A	ENSP00000344215.4
	TP53INP1	ENST00000448464.6	TSL:1	c.-151+2745G>C		intron	N/A	ENSP00000390063.2
	NDUFAF6	ENST00000396113.5	TSL:5	c.-799+790C>G		intron	N/A	ENSP00000379419.1

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

African (AFR) AF: 0.204 AC: 8418 AN: 41354

American (AMR) AF: 0.385 AC: 5868 AN: 15244

Ashkenazi Jewish (ASJ) AF: 0.372 AC: 1288 AN: 3460

East Asian (EAS) AF: 0.166 AC: 857 AN: 5150

South Asian (SAS) AF: 0.321 AC: 1536 AN: 4784

European-Finnish (FIN) AF: 0.400 AC: 4206 AN: 10502

Middle Eastern (MID) AF: 0.405 AC: 119 AN: 294

European-Non Finnish (NFE) AF: 0.410 AC: 27797 AN: 67856

Other (OTH) AF: 0.326 AC: 685 AN: 2100

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	2.0
DANN	Benign	0.50
PhyloP100		-0.36
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: rs1713669; hg19: chr8-95958637;