rs1555602657

Variant names:

• chr16-53648966-ACTGCATATG-A
• rs1555602657
• NM_015272.5:c.2293_2301delCATATGCAG

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PM2 PM4

The NM_015272.5(RPGRIP1L):​c.2293_2301delCATATGCAG​(p.His765_Gln767del) variant causes a conservative inframe deletion change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★). Synonymous variant affecting the same amino acid position (i.e. H765H) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: RPGRIP1L NM_015272.5 conservative_inframe_deletion
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.95
• Publications: 0 publications found

Genes affected

RPGRIP1L (HGNC:29168): (RPGRIP1 like) The protein encoded by this gene can localize to the basal body-centrosome complex or to primary cilia and centrosomes in ciliated cells. The encoded protein has been found to interact with nephrocystin-4. Defects in this gene are a cause of Joubert syndrome type 7 (JBTS7) and Meckel syndrome type 5 (MKS5). [provided by RefSeq, Jun 2016]

RPGRIP1L Gene-Disease associations (from GenCC):

• Meckel syndrome, type 5

  Inheritance: AR Classification: DEFINITIVE Submitted by: G2P
• Joubert syndrome 7

  Inheritance: AR Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)
• COACH syndrome 1

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
• Joubert syndrome with renal defect

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
• Meckel syndrome

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Uncertain_significance. The variant received 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PM4: Nonframeshift variant in NON repetitive region in NM_015272.5.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_015272.5. 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
	RPGRIP1L	NM_015272.5	MANE Select	c.2293_2301delCATATGCAG	p.His765_Gln767del	conservative_inframe_deletion	Exon 16 of 27	NP_056087.2
	RPGRIP1L	NM_001330538.2		c.2293_2301delCATATGCAG	p.His765_Gln767del	conservative_inframe_deletion	Exon 16 of 26	NP_001317467.1
	RPGRIP1L	NM_001308334.3		c.2293_2301delCATATGCAG	p.His765_Gln767del	conservative_inframe_deletion	Exon 16 of 26	NP_001295263.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RPGRIP1L	ENST00000647211.2	MANE Select	c.2293_2301delCATATGCAG	p.His765_Gln767del	conservative_inframe_deletion	Exon 16 of 27	ENSP00000493946.1
	RPGRIP1L	ENST00000563746.5	TSL:1	c.2293_2301delCATATGCAG	p.His765_Gln767del	conservative_inframe_deletion	Exon 16 of 26	ENSP00000457889.1
	RPGRIP1L	ENST00000621565.5	TSL:1	c.2293_2301delCATATGCAG	p.His765_Gln767del	conservative_inframe_deletion	Exon 16 of 26	ENSP00000480698.1

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

ClinVar submissions as Germline

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	Meckel-Gruber syndrome;C0431399:Joubert syndrome (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		3.9

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs1555602657; hg19: chr16-53682878;