rs568801926

Variant names:

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

Your query was ambiguous. Multiple possible variants found:

• chr16-53622339-G-A
• chr16-53622339-G-C

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_Strong BP6 BP7

The NM_015272.5(RPGRIP1L):​c.3312C>T​(p.Pro1104Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000523 in 632,882 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 Conflicting classifications of pathogenicity (no stars). Synonymous variant affecting the same amino acid position (i.e. P1104P) has been classified as Likely benign.

• Frequency:
  • Genomes: 𝑓 0.00044 (0 hom., cov: 30)
  • Exomes 𝑓: 0.00055 (0 hom.)
• Consequence: RPGRIP1L NM_015272.5 synonymous
• Clinical Significance: Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:3 B:6
• 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):

• 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 -6 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BP6: Variant 16-53622339-G-A is Benign according to our data. Variant chr16-53622339-G-A is described in ClinVar as Conflicting_classifications_of_pathogenicity. ClinVar VariationId is 260604.
• BP7: Synonymous conserved (PhyloP=0.229 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.3312C>T	p.Pro1104Pro	synonymous	Exon 23 of 27	NP_056087.2	Q68CZ1-1
	RPGRIP1L	NM_001330538.2		c.3210C>T	p.Pro1070Pro	synonymous	Exon 22 of 26	NP_001317467.1	H3BV03
	RPGRIP1L	NM_001308334.3		c.3295-3131C>T		intron	N/A	NP_001295263.1	A0A087WX34

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RPGRIP1L	ENST00000647211.2	MANE Select	c.3312C>T	p.Pro1104Pro	synonymous	Exon 23 of 27	ENSP00000493946.1	Q68CZ1-1
	RPGRIP1L	ENST00000563746.5	TSL:1	c.3210C>T	p.Pro1070Pro	synonymous	Exon 22 of 26	ENSP00000457889.1	H3BV03
	RPGRIP1L	ENST00000621565.5	TSL:1	c.3295-3131C>T		intron	N/A	ENSP00000480698.1	A0A087WX34

Frequencies

GnomAD3 genomes AF: 0.000443 AC: 67 AN: 151408 Hom.: 0 Cov.: 30

Gnomad AFR AF: 0.0000729

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000394

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00115

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000677

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000362 AC: 33 AN: 91274 AF XY: 0.000355

Gnomad AFR exome AF: 0.000271

Gnomad AMR exome AF: 0.000168

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.000431

Gnomad NFE exome AF: 0.000749

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.000548 AC: 264 AN: 481474 Hom.: 0 Cov.: 0 AF XY: 0.000449 AC XY: 116 AN XY: 258220

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

American (AMR) AF: 0.000132 AC: 4 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: 0.0000959 AC: 5 AN: 52130

European-Finnish (FIN) AF: 0.000778 AC: 23 AN: 29548

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

European-Non Finnish (NFE) AF: 0.000795 AC: 222 AN: 279236

Other (OTH) AF: 0.000366 AC: 10 AN: 27308

GnomAD4 genome AF: 0.000443 AC: 67 AN: 151408 Hom.: 0 Cov.: 30 AF XY: 0.000447 AC XY: 33 AN XY: 73850

African (AFR) AF: 0.0000729 AC: 3 AN: 41160

American (AMR) AF: 0.000394 AC: 6 AN: 15214

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5146

South Asian (SAS) AF: 0.00 AC: 0 AN: 4796

European-Finnish (FIN) AF: 0.00115 AC: 12 AN: 10402

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 314

European-Non Finnish (NFE) AF: 0.000677 AC: 46 AN: 67928

Other (OTH) AF: 0.00 AC: 0 AN: 2068

Alfa AF: 0.000323 Hom.: 0

Bravo AF: 0.000336

ClinVar

ClinVar submissions

Significance: Conflicting classifications of pathogenicity

Revision: criteria provided, conflicting classifications

Pathogenic	VUS	Benign	Condition
-	-	3	not provided (3)
-	-	2	not specified (2)
-	1	-	Joubert syndrome 7 (1)
-	1	-	Meckel syndrome, type 5 (1)
-	-	1	Meckel-Gruber syndrome;C5979921:Joubert syndrome (1)
-	1	-	Nephronophthisis 8 (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	5.2
DANN	Benign	0.56
PhyloP100		0.23

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: rs568801926; hg19: chr16-53656251;