GIPC1 p.Ala284Ala

Variant names:

• chr19-14478565-C-C
• NM_005716.4:c.

Your query was ambiguous. Multiple possible variants found:

• chr19-14478566--
• chr19-14478566-C-A
• chr19-14478566-C-G
• chr19-14478566-C-T

Variant summary

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

The NM_005716.4(GIPC1):​c. variant causes a splice region, exon region change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: GIPC1 NM_005716.4 splice_region, exon_region
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.762
• Publications: 0 publications found

Genes affected

GIPC1 (HGNC:1226): (GIPC PDZ domain containing family member 1) GIPC1 is a scaffolding protein that regulates cell surface receptor expression and trafficking (Lee et al., 2008 [PubMed 18775991]).[supplied by OMIM, Apr 2009]

GIPC1 Gene-Disease associations (from GenCC):

• oculopharyngodistal myopathy 2

  Inheritance: AD Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)
• oculopharyngodistal myopathy

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

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

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005716.4. 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
	GIPC1	NM_005716.4	MANE Select	c.		splice_region exon_region	Exon 9 of 9	NP_005707.1	O14908-1
	GIPC1	NM_202468.3		c.		splice_region exon_region	Exon 8 of 8	NP_974197.1	O14908-1
	GIPC1	NM_202470.3		c.		splice_region exon_region	Exon 7 of 7	NP_974199.1	O14908-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GIPC1	ENST00000393033.9	TSL:1 MANE Select	c.		splice_region exon_region	Exon 9 of 9	ENSP00000376753.3	O14908-1
	GIPC1	ENST00000345425.6	TSL:1	c.		splice_region exon_region	Exon 7 of 7	ENSP00000340698.1	O14908-1
	GIPC1	ENST00000586027.5	TSL:2	c.		splice_region exon_region	Exon 8 of 8	ENSP00000466747.1	O14908-1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 34

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		-0.76

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: chr19-14589377;