rs8396

Variant names:

• chr4-158709665-T-A
• rs8396
• NM_005038.3:c.*71A>T

Your query was ambiguous. Multiple possible variants found:

• chr4-158709665-T-A
• chr4-158709665-T-C

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_005038.3(PPID):​c.*71A>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000383 in 1,044,986 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: 32)
  • Exomes 𝑓: 0.0000038 (0 hom.)
• Consequence: PPID NM_005038.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.01
• Publications: 0 publications found

Genes affected

PPID (HGNC:9257): (peptidylprolyl isomerase D) The protein encoded by this gene is a member of the peptidyl-prolyl cis-trans isomerase (PPIase) family. PPIases catalyze the cis-trans isomerization of proline imidic peptide bonds in oligopeptides and accelerate the folding of proteins. This protein has been shown to possess PPIase activity and, similar to other family members, can bind to the immunosuppressant cyclosporin A. [provided by RefSeq, Jul 2008]

ETFDH (HGNC:3483): (electron transfer flavoprotein dehydrogenase) This gene encodes a component of the electron-transfer system in mitochondria and is essential for electron transfer from a number of mitochondrial flavin-containing dehydrogenases to the main respiratory chain. Mutations in this gene are associated with glutaric acidemia. Alternatively spliced transcript variants that encode distinct isoforms have been observed. [provided by RefSeq, Aug 2013]

ETFDH Gene-Disease associations (from GenCC):

• multiple acyl-CoA dehydrogenase deficiency

  Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: G2P, Labcorp Genetics (formerly Invitae), PanelApp Australia, ClinGen, Ambry Genetics

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PPID	NM_005038.3	c.*71A>T		3_prime_UTR_variant	Exon 10 of 10	ENST00000307720.4	NP_005029.1
ETFDH	NM_004453.4	c.*1138T>A		downstream_gene_variant		ENST00000511912.6	NP_004444.2
ETFDH	NM_001281737.2	c.*1138T>A		downstream_gene_variant			NP_001268666.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PPID	ENST00000307720.4	c.*71A>T		3_prime_UTR_variant	Exon 10 of 10	1	NM_005038.3	ENSP00000303754.3
ETFDH	ENST00000511912.6	c.*1138T>A		downstream_gene_variant		1	NM_004453.4	ENSP00000426638.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000383 AC: 4 AN: 1044986 Hom.: 0 Cov.: 13 AF XY: 0.00000563 AC XY: 3 AN XY: 532454

African (AFR) AF: 0.00 AC: 0 AN: 24594

American (AMR) AF: 0.00 AC: 0 AN: 34692

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 21894

East Asian (EAS) AF: 0.00 AC: 0 AN: 36766

South Asian (SAS) AF: 0.00 AC: 0 AN: 71070

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 42484

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4682

European-Non Finnish (NFE) AF: 0.00000525 AC: 4 AN: 762494

Other (OTH) AF: 0.00 AC: 0 AN: 46310

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	0.32
DANN	Benign	0.58
PhyloP100		-1.0

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: rs8396; hg19: chr4-159630817;