NM_015272.5:c.3312C>G

Variant names:

• chr16-53622339-G-C
• rs568801926
• NM_015272.5:c.3312C>G

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 2P and 7B. PM2 BP4_Strong BP6_Moderate BP7

The NM_015272.5(RPGRIP1L):​c.3312C>G​(p.Pro1104Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000104 in 481,482 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★). Synonymous variant affecting the same amino acid position (i.e. P1104P) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 30)
  • Exomes 𝑓: 0.000010 (0 hom.)
• Consequence: RPGRIP1L NM_015272.5 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.229
• 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: Likely_benign. The variant received -5 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BP6: Variant 16-53622339-G-C is Benign according to our data. Variant chr16-53622339-G-C is described in ClinVar as Likely_benign. ClinVar VariationId is 461758.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=0.229 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RPGRIP1L	NM_015272.5	c.3312C>G	p.Pro1104Pro	synonymous_variant	Exon 23 of 27	ENST00000647211.2	NP_056087.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RPGRIP1L	ENST00000647211.2	c.3312C>G	p.Pro1104Pro	synonymous_variant	Exon 23 of 27		NM_015272.5	ENSP00000493946.1

Frequencies

GnomAD3 genomes Cov.: 30

GnomAD4 exome AF: 0.0000104 AC: 5 AN: 481482 Hom.: 0 Cov.: 0 AF XY: 0.00000387 AC XY: 1 AN XY: 258226

African (AFR) AF: 0.00 AC: 0 AN: 13482

American (AMR) AF: 0.00 AC: 0 AN: 30192

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 18200

East Asian (EAS) AF: 0.00 AC: 0 AN: 29080

South Asian (SAS) AF: 0.00 AC: 0 AN: 52132

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 29548

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2298

European-Non Finnish (NFE) AF: 0.0000179 AC: 5 AN: 279242

Other (OTH) AF: 0.00 AC: 0 AN: 27308

GnomAD4 genome Cov.: 30

Alfa AF: 0.00 Hom.: 0

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Meckel-Gruber syndrome;C0431399:Joubert syndrome Benign:1

Nov 15, 2023

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	1.3
DANN	Benign	0.48
PhyloP100		0.23

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		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: rs568801926; hg19: chr16-53656251;