1-43545153-C-A

Variant names:

• chr1-43545153-C-A
• rs201337870
• NM_002840.5:c.78C>A

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 2P and 3B. PM2 BP4_Moderate BP7

The NM_002840.5(PTPRF):​c.78C>A​(p.Gly26Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000021 in 1,428,366 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. Synonymous variant affecting the same amino acid position (i.e. G26G) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: PTPRF NM_002840.5 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.40
• Publications: 0 publications found

Genes affected

PTPRF (HGNC:9670): (protein tyrosine phosphatase receptor type F) The protein encoded by this gene is a member of the protein tyrosine phosphatase (PTP) family. PTPs are known to be signaling molecules that regulate a variety of cellular processes including cell growth, differentiation, mitotic cycle, and oncogenic transformation. This PTP possesses an extracellular region, a single transmembrane region, and two tandem intracytoplasmic catalytic domains, and thus represents a receptor-type PTP. The extracellular region contains three Ig-like domains, and nine non-Ig like domains similar to that of neural-cell adhesion molecule. This PTP was shown to function in the regulation of epithelial cell-cell contacts at adherents junctions, as well as in the control of beta-catenin signaling. An increased expression level of this protein was found in the insulin-responsive tissue of obese, insulin-resistant individuals, and may contribute to the pathogenesis of insulin resistance. Two alternatively spliced transcript variants of this gene, which encode distinct proteins, have been reported. [provided by RefSeq, Jul 2008]

PTPRF Gene-Disease associations (from GenCC):

• breasts and/or nipples, aplasia or hypoplasia of, 2

  Inheritance: AR Classification: STRONG, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), G2P

ACMG classification

Our verdict: Likely_benign. The variant received -1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.28).
• BP7: Synonymous conserved (PhyloP=-1.4 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002840.5. 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
	PTPRF	NM_002840.5	MANE Select	c.78C>A	p.Gly26Gly	synonymous	Exon 3 of 34	NP_002831.2	P10586-1
	PTPRF	NM_130440.4		c.78C>A	p.Gly26Gly	synonymous	Exon 3 of 33	NP_569707.2	P10586-2
	PTPRF	NM_001329138.2		c.78C>A	p.Gly26Gly	synonymous	Exon 4 of 37	NP_001316067.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PTPRF	ENST00000359947.9	TSL:1 MANE Select	c.78C>A	p.Gly26Gly	synonymous	Exon 3 of 34	ENSP00000353030.4	P10586-1
	PTPRF	ENST00000438120.5	TSL:1	c.78C>A	p.Gly26Gly	synonymous	Exon 3 of 33	ENSP00000398822.1	P10586-2
	PTPRF	ENST00000437607.1	TSL:1	c.78C>A	p.Gly26Gly	synonymous	Exon 1 of 6	ENSP00000413306.1	A2A437

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000210 AC: 3 AN: 1428366 Hom.: 0 Cov.: 30 AF XY: 0.00000283 AC XY: 2 AN XY: 707586

African (AFR) AF: 0.00 AC: 0 AN: 32642

American (AMR) AF: 0.00 AC: 0 AN: 40294

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25468

East Asian (EAS) AF: 0.00 AC: 0 AN: 37818

South Asian (SAS) AF: 0.00 AC: 0 AN: 81326

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 51196

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5736

European-Non Finnish (NFE) AF: 0.00000274 AC: 3 AN: 1094862

Other (OTH) AF: 0.00 AC: 0 AN: 59024

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.28
CADD	Benign	0.99
DANN	Benign	0.67
PhyloP100		-1.4
PromoterAI		0.00060	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=100/0	polymorphism

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: rs201337870; hg19: chr1-44010824;