16-1984275-G-T

Variant names:

• chr16-1984275-G-T
• NM_005262.3:c.57G>T
• GFER p.Pro19Pro

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP7

The NM_005262.3(GFER):​c.57G>T​(p.Pro19Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. 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. Synonymous variant affecting the same amino acid position (i.e. P19P) has been classified as Benign.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: GFER NM_005262.3 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -4.02
• Publications: 0 publications found

Genes affected

GFER (HGNC:4236): (growth factor, augmenter of liver regeneration) The hepatotrophic factor designated augmenter of liver regeneration (ALR) is thought to be one of the factors responsible for the extraordinary regenerative capacity of mammalian liver. It has also been called hepatic regenerative stimulation substance (HSS). The gene resides on chromosome 16 in the interval containing the locus for polycystic kidney disease (PKD1). The putative gene product is 42% similar to the scERV1 protein of yeast. The yeast scERV1 gene had been found to be essential for oxidative phosphorylation, the maintenance of mitochondrial genomes, and the cell division cycle. The human gene is both the structural and functional homolog of the yeast scERV1 gene. [provided by RefSeq, Jul 2008]

NOXO1 (HGNC:19404): (NADPH oxidase organizer 1) This gene encodes an NADPH oxidase (NOX) organizer, which positively regulates NOX1 and NOX3. The protein contains a PX domain and two SH3 domains. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene. [provided by RefSeq, Jun 2012]

ACMG classification

Our verdict: Likely_benign. The variant received -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.55).
• BP7: Synonymous conserved (PhyloP=-4.02 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005262.3. 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
	GFER	NM_005262.3	MANE Select	c.57G>T	p.Pro19Pro	synonymous	Exon 1 of 3	NP_005253.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GFER	ENST00000248114.7	TSL:1 MANE Select	c.57G>T	p.Pro19Pro	synonymous	Exon 1 of 3	ENSP00000248114.6	P55789-1
	GFER	ENST00000561710.1	TSL:2	c.18G>T	p.Pro6Pro	synonymous	Exon 1 of 2	ENSP00000456189.1	H3BRD2
	GFER	ENST00000569451.1	TSL:5	c.57G>T	p.Pro19Pro	synonymous	Exon 1 of 2	ENSP00000456432.1	H3BRW3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1325028 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 652766

African (AFR) AF: 0.00 AC: 0 AN: 26462

American (AMR) AF: 0.00 AC: 0 AN: 26600

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 23042

East Asian (EAS) AF: 0.00 AC: 0 AN: 30356

South Asian (SAS) AF: 0.00 AC: 0 AN: 72654

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 32988

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4876

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1053164

Other (OTH) AF: 0.00 AC: 0 AN: 54886

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.55
CADD	Benign	4.7
DANN	Benign	0.81
PhyloP100		-4.0
PromoterAI		0.024	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr16-2034276;