3-47381198-C-G

Variant names:

• chr3-47381198-C-G
• rs879446639
• NM_015466.4:c.84+18C>G

Variant summary

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

The NM_015466.4(PTPN23):​c.84+18C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000706 in 1,416,014 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: 7.1e-7 (0 hom.)
• Consequence: PTPN23 NM_015466.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0270
• Publications: 0 publications found

Genes affected

PTPN23 (HGNC:14406): (protein tyrosine phosphatase non-receptor type 23) This gene encodes a member of the non-receptor type protein-tyrosine phosphatase family. The encoded protein may be involved in the regulation of small nuclear ribonucleo protein assembly and pre-mRNA splicing by modifying the survival motor neuron (SMN) complex. The encoded protein additionally plays a role in ciliogenesis and is part of endosomal sorting complex required for transport (ESCRT) pathways. This gene may serve a tumor suppressor function. [provided by RefSeq, Jul 2016]

PTPN23-DT (HGNC:55397): (PTPN23 divergent transcript)

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=-0.75).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_015466.4. 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
	PTPN23	NM_015466.4	MANE Select	c.84+18C>G		intron	N/A	NP_056281.1	Q9H3S7
	PTPN23	NM_001304482.2		c.-167+18C>G		intron	N/A	NP_001291411.1	B4DST5
	PTPN23-DT	NR_185912.1		n.295G>C		non_coding_transcript_exon	Exon 1 of 1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PTPN23	ENST00000265562.5	TSL:1 MANE Select	c.84+18C>G		intron	N/A	ENSP00000265562.4	Q9H3S7
	PTPN23	ENST00000889694.1		c.84+18C>G		intron	N/A	ENSP00000559753.1
	PTPN23	ENST00000918778.1		c.84+18C>G		intron	N/A	ENSP00000588837.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 7.06e-7 AC: 1 AN: 1416014 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 700304

African (AFR) AF: 0.00 AC: 0 AN: 32114

American (AMR) AF: 0.00 AC: 0 AN: 37892

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25290

East Asian (EAS) AF: 0.00 AC: 0 AN: 36590

South Asian (SAS) AF: 0.00 AC: 0 AN: 80394

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 50318

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5718

European-Non Finnish (NFE) AF: 9.18e-7 AC: 1 AN: 1089042

Other (OTH) AF: 0.00 AC: 0 AN: 58656

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.75
CADD	Benign	6.7
DANN	Benign	0.58
PhyloP100		0.027
PromoterAI		-0.019	Neutral

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: rs879446639; hg19: chr3-47422688;