rs75917719

Variant names:

• chr8-94940213-G-A
• rs75917719
• NM_033285.4:c.120C>T

Your query was ambiguous. Multiple possible variants found:

• chr8-94940213-G-A
• chr8-94940213-G-C

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP7 BS1 BS2

The NM_033285.4(TP53INP1):​c.120C>T​(p.Cys40Cys) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0175 in 1,608,368 control chromosomes in the GnomAD database, including 337 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 0.023 (58 hom., cov: 32)
  • Exomes 𝑓: 0.017 (279 hom.)
• Consequence: TP53INP1 NM_033285.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.87

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 -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.48).
• BP7: Synonymous conserved (PhyloP=2.87 with no splicing effect.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0231 (3513/152248) while in subpopulation AFR AF= 0.0407 (1689/41532). AF 95% confidence interval is 0.0391. There are 58 homozygotes in gnomad4. There are 1623 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 58 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TP53INP1	NM_033285.4	c.120C>T	p.Cys40Cys	synonymous_variant	Exon 3 of 4	ENST00000342697.5	NP_150601.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TP53INP1	ENST00000342697.5	c.120C>T	p.Cys40Cys	synonymous_variant	Exon 3 of 4	1	NM_033285.4	ENSP00000344215.4

Frequencies

GnomAD3 genomes AF: 0.0231 AC: 3513 AN: 152130 Hom.: 58 Cov.: 32

Gnomad AFR AF: 0.0408

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0207

Gnomad ASJ AF: 0.0173

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00580

Gnomad FIN AF: 0.00943

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.0184

Gnomad OTH AF: 0.0315

GnomAD3 exomes AF: 0.0144 AC: 3488 AN: 242580 Hom.: 40 AF XY: 0.0136 AC XY: 1785 AN XY: 131534

Gnomad AFR exome AF: 0.0416

Gnomad AMR exome AF: 0.0123

Gnomad ASJ exome AF: 0.0163

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00551

Gnomad FIN exome AF: 0.00917

Gnomad NFE exome AF: 0.0165

Gnomad OTH exome AF: 0.0197

GnomAD4 exome AF: 0.0170 AC: 24709 AN: 1456120 Hom.: 279 Cov.: 31 AF XY: 0.0166 AC XY: 12002 AN XY: 723920

Gnomad4 AFR exome AF: 0.0419

Gnomad4 AMR exome AF: 0.0128

Gnomad4 ASJ exome AF: 0.0187

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00515

Gnomad4 FIN exome AF: 0.0103

Gnomad4 NFE exome AF: 0.0180

Gnomad4 OTH exome AF: 0.0197

GnomAD4 genome AF: 0.0231 AC: 3513 AN: 152248 Hom.: 58 Cov.: 32 AF XY: 0.0218 AC XY: 1623 AN XY: 74458

Gnomad4 AFR AF: 0.0407

Gnomad4 AMR AF: 0.0207

Gnomad4 ASJ AF: 0.0173

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00580

Gnomad4 FIN AF: 0.00943

Gnomad4 NFE AF: 0.0184

Gnomad4 OTH AF: 0.0312

Alfa AF: 0.0171 Hom.: 13

Bravo AF: 0.0250

Asia WGS AF: 0.00549 AC: 19 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.48
CADD	Benign	9.4
DANN	Benign	0.71
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.10		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: rs75917719; hg19: chr8-95952441;