rs948791022

Variant names:

• chr16-69330428-T-A
• rs948791022
• NM_022341.2:c.143A>T

Your query was ambiguous. Multiple possible variants found:

• chr16-69330428-T-A
• chr16-69330428-T-C
• chr16-69330428-T-G

Variant summary

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

The NM_022341.2(PDF):​c.143A>T​(p.Tyr48Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000755 in 1,324,094 control chromosomes in the GnomAD database, with no homozygous occurrence. 14/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. Y48C) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 7.6e-7 (0 hom.)
• Consequence: PDF NM_022341.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.55
• Publications: 0 publications found

Genes affected

PDF (HGNC:30012): (peptide deformylase, mitochondrial) Protein synthesis proceeds after formylation of methionine by methionyl-tRNA formyl transferase (FMT) and transfer of the charged initiator f-met tRNA to the ribosome. In eubacteria and eukaryotic organelles the product of this gene, peptide deformylase (PDF), removes the formyl group from the initiating methionine of nascent peptides. In eubacteria, deformylation of nascent peptides is required for subsequent cleavage of initiating methionines by methionine aminopeptidase. The discovery that a natural inhibitor of PDF, actinonin, acts as an antimicrobial agent in some bacteria has spurred intensive research into the design of bacterial-specific PDF inhibitors. In human cells, only mitochondrial proteins have N-formylation of initiating methionines. Protein inhibitors of PDF or siRNAs of PDF block the growth of cancer cell lines but have no effect on normal cell growth. In humans, PDF function may therefore be restricted to rapidly growing cells. [provided by RefSeq, Nov 2008]

COG8 (HGNC:18623): (component of oligomeric golgi complex 8) This gene encodes a protein that is a component of the conserved oligomeric Golgi (COG) complex, a multiprotein complex that plays a structural role in the Golgi apparatus, and is involved in intracellular membrane trafficking and glycoprotein modification. Mutations in this gene cause congenital disorder of glycosylation, type IIh, a disease that is characterized by under-glycosylated serum proteins, and whose symptoms include severe psychomotor retardation, failure to thrive, seizures, and dairy and wheat product intolerance. [provided by RefSeq, Jul 2008]

COG8 Gene-Disease associations (from GenCC):

• COG8-congenital disorder of glycosylation

  Inheritance: AR Classification: STRONG, MODERATE, SUPPORTIVE Submitted by: Ambry Genetics, PanelApp Australia, Orphanet, Labcorp Genetics (formerly Invitae)

ENSG00000272617 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PDF	NM_022341.2	c.143A>T	p.Tyr48Phe	missense_variant	Exon 1 of 2	ENST00000288022.2	NP_071736.1
COG8	NM_032382.5	c.*26+385A>T		intron_variant	Intron 5 of 5	ENST00000306875.10	NP_115758.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PDF	ENST00000288022.2	c.143A>T	p.Tyr48Phe	missense_variant	Exon 1 of 2	1	NM_022341.2	ENSP00000288022.1
COG8	ENST00000306875.10	c.*26+385A>T		intron_variant	Intron 5 of 5	1	NM_032382.5	ENSP00000305459.6
ENSG00000272617	ENST00000562949.1	c.352-1249A>T		intron_variant	Intron 1 of 1	3		ENSP00000457718.1
COG8	ENST00000562595.5	c.548+4898A>T		intron_variant	Intron 3 of 3	5		ENSP00000456705.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 7.55e-7 AC: 1 AN: 1324094 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 653124

African (AFR) AF: 0.00 AC: 0 AN: 26692

American (AMR) AF: 0.00 AC: 0 AN: 26680

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 23344

East Asian (EAS) AF: 0.00 AC: 0 AN: 28604

South Asian (SAS) AF: 0.0000136 AC: 1 AN: 73438

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 32890

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3910

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1053616

Other (OTH) AF: 0.00 AC: 0 AN: 54920

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.19
BayesDel_addAF	Benign	-0.078	T
BayesDel_noAF	Benign	-0.35
CADD	Benign	21
DANN	Benign	0.93
DEOGEN2	Benign	0.0059	T
Eigen	Benign	-0.040
Eigen_PC	Benign	-0.055
FATHMM_MKL	Benign	0.49	N
LIST_S2	Benign	0.60	T
M_CAP	Pathogenic	0.66	D
MetaRNN	Uncertain	0.53	D
MetaSVM	Benign	-0.90	T
MutationAssessor	Benign	0.90	L
PhyloP100		1.6
PrimateAI	Pathogenic	0.88	D
PROVEAN	Benign	-0.67	N
REVEL	Benign	0.10
Sift	Benign	0.11	T
Sift4G	Uncertain	0.052	T
Polyphen		0.89	P
Vest4		0.45
MutPred		0.32		Gain of disorder (P = 0.0786);
MVP		0.57
MPC		0.67
ClinPred		0.51	D
GERP RS		2.8
PromoterAI		-0.039	Neutral
Varity_R		0.12
gMVP		0.37

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: rs948791022; hg19: chr16-69364331;