chr8-94926194-C-G

Variant names:

• chr8-94926194-C-G
• rs7760
• NM_033285.4:c.*4285G>C

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_033285.4(TP53INP1):​c.*4285G>C variant causes a 3 prime UTR change. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 31)
• Consequence: TP53INP1 NM_033285.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.64
• Publications: 11 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 disease

  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: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.29).

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TP53INP1	NM_033285.4	MANE Select	c.*4285G>C		3_prime_UTR	Exon 4 of 4	NP_150601.1	Q96A56-1
	TP53INP1	NM_001135733.2		c.*4551G>C		3_prime_UTR	Exon 5 of 5	NP_001129205.1	Q96A56-2
	NDUFAF6	NM_001354516.2		c.-264+30267C>G		intron	N/A	NP_001341445.1	Q330K2-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TP53INP1	ENST00000342697.5	TSL:1 MANE Select	c.*4285G>C		3_prime_UTR	Exon 4 of 4	ENSP00000344215.4	Q96A56-1
	TP53INP1	ENST00000448464.6	TSL:1	c.*4551G>C		3_prime_UTR	Exon 5 of 5	ENSP00000390063.2	Q96A56-2
	TP53INP1	ENST00000942548.1		c.*4285G>C		3_prime_UTR	Exon 5 of 5	ENSP00000612607.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 0

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.29
CADD	Benign	14
DANN	Benign	0.88
PhyloP100		3.6

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: rs7760; hg19: chr8-95938422;