chr16-53687846-C-CA

Variant names:

• chr16-53687846-C-CA
• rs559978421
• NM_015272.5:c.632+16dupT

Variant summary

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

The NM_015272.5(RPGRIP1L):​c.632+16dupT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000752 in 1,330,498 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 7.5e-7 (0 hom.)
• Consequence: RPGRIP1L NM_015272.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.350
• 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):

• ciliopathy

  Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
• 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 2 ACMG points.

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

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.632+16dupT		intron	N/A	NP_056087.2
	RPGRIP1L	NM_001330538.2		c.632+16dupT		intron	N/A	NP_001317467.1
	RPGRIP1L	NM_001308334.3		c.632+16dupT		intron	N/A	NP_001295263.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RPGRIP1L	ENST00000647211.2	MANE Select	c.632+16_632+17insT		intron	N/A	ENSP00000493946.1
	RPGRIP1L	ENST00000563746.5	TSL:1	c.632+16_632+17insT		intron	N/A	ENSP00000457889.1
	RPGRIP1L	ENST00000621565.5	TSL:1	c.632+16_632+17insT		intron	N/A	ENSP00000480698.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 7.52e-7 AC: 1 AN: 1330498 Hom.: 0 Cov.: 21 AF XY: 0.00 AC XY: 0 AN XY: 669750

African (AFR) AF: 0.00 AC: 0 AN: 30816

American (AMR) AF: 0.00 AC: 0 AN: 44460

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25230

East Asian (EAS) AF: 0.00 AC: 0 AN: 38846

South Asian (SAS) AF: 0.00 AC: 0 AN: 83172

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53212

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5436

European-Non Finnish (NFE) AF: 0.00000101 AC: 1 AN: 993336

Other (OTH) AF: 0.00 AC: 0 AN: 55990

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.35

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: rs559978421; hg19: chr16-53721758;