rs775153934

Variant names:

• chr16-53645650-C-A
• rs775153934
• NM_015272.5:c.2658G>T

Your query was ambiguous. Multiple possible variants found:

• chr16-53645650-C-A
• chr16-53645650-C-T

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2 BP4_Moderate BP6_Moderate BP7

The NM_015272.5(RPGRIP1L):​c.2658G>T​(p.Ser886Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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. S886S) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: RPGRIP1L NM_015272.5 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.71
• Publications: 1 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, STRONG Submitted by: PanelApp Australia, 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: Likely_benign. The variant received -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.35).
• BP6: Variant 16-53645650-C-A is Benign according to our data. Variant chr16-53645650-C-A is described in ClinVar as Likely_benign. ClinVar VariationId is 2129310.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-1.71 with no splicing effect.

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.2658G>T	p.Ser886Ser	synonymous	Exon 17 of 27	NP_056087.2	Q68CZ1-1
	RPGRIP1L	NM_001330538.2		c.2658G>T	p.Ser886Ser	synonymous	Exon 17 of 26	NP_001317467.1	H3BV03
	RPGRIP1L	NM_001308334.3		c.2658G>T	p.Ser886Ser	synonymous	Exon 17 of 26	NP_001295263.1	A0A087WX34

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RPGRIP1L	ENST00000647211.2	MANE Select	c.2658G>T	p.Ser886Ser	synonymous	Exon 17 of 27	ENSP00000493946.1	Q68CZ1-1
	RPGRIP1L	ENST00000563746.5	TSL:1	c.2658G>T	p.Ser886Ser	synonymous	Exon 17 of 26	ENSP00000457889.1	H3BV03
	RPGRIP1L	ENST00000621565.5	TSL:1	c.2658G>T	p.Ser886Ser	synonymous	Exon 17 of 26	ENSP00000480698.1	A0A087WX34

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

ClinVar submissions

Significance: Likely benign

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
BayesDel_noAF	Benign	-0.35
CADD	Benign	0.73
DANN	Benign	0.54
PhyloP100		-1.7

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs775153934; hg19: chr16-53679562;