19-49447460-GC-TG

Variant names:

• chr19-49447460-GC-TG
• NM_017916.3:c.488_489delGCinsCA
• PIH1D1 p.Arg163Pro

Variant summary

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

The NM_017916.3(PIH1D1):​c.488_489delGCinsCA​(p.Arg163Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. It is difficult to determine the true allele frequency of this variant because it is of type MNV, and the frequency of such variant types in population databases may be underestimated and unreliable. 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. R163H) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: PIH1D1 NM_017916.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.78
• Publications: 0 publications found

Genes affected

PIH1D1 (HGNC:26075): (PIH1 domain containing 1) Enables several functions, including RNA polymerase I core promoter sequence-specific DNA binding activity; enzyme binding activity; and phosphoprotein binding activity. Involved in several processes, including box C/D snoRNP assembly; positive regulation of signal transduction; and regulation of cellular protein metabolic process. Located in cytoplasm and nucleolus. Part of R2TP complex and pre-snoRNP complex. [provided by Alliance of Genome Resources, Apr 2022]

ENSG00000305589 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_017916.3. 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
	PIH1D1	NM_017916.3	MANE Select	c.488_489delGCinsCA	p.Arg163Pro	missense	N/A	NP_060386.1	Q9NWS0-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PIH1D1	ENST00000262265.10	TSL:1 MANE Select	c.488_489delGCinsCA	p.Arg163Pro	missense	N/A	ENSP00000262265.4	Q9NWS0-1
	PIH1D1	ENST00000943281.1		c.488_489delGCinsCA	p.Arg163Pro	missense	N/A	ENSP00000613340.1
	PIH1D1	ENST00000911068.1		c.539_540delGCinsCA	p.Arg180Pro	missense	N/A	ENSP00000581127.1

Frequencies

GnomAD3 genomes Cov.: 32

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		1.8

Splicing

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: chr19-49950717;