chr16-53601339-A-C

Variant names:

• chr16-53601339-A-C
• rs3760008
• NM_015272.5:c.*737T>G

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_015272.5(RPGRIP1L):​c.*737T>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.381 in 152,274 control chromosomes in the GnomAD database, including 12,814 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.38 (12812 hom., cov: 33)
  • Exomes 𝑓: 0.20 (2 hom.)
• Consequence: RPGRIP1L NM_015272.5 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: -0.338
• Publications: 11 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: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BP6: Variant 16-53601339-A-C is Benign according to our data. Variant chr16-53601339-A-C is described in ClinVar as Benign. ClinVar VariationId is 319634.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.592 is higher than 0.05.

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.*737T>G		3_prime_UTR	Exon 27 of 27	NP_056087.2	Q68CZ1-1
	RPGRIP1L	NM_001330538.2		c.*737T>G		3_prime_UTR	Exon 26 of 26	NP_001317467.1	H3BV03
	RPGRIP1L	NM_001308334.3		c.*737T>G		3_prime_UTR	Exon 26 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.*737T>G		3_prime_UTR	Exon 27 of 27	ENSP00000493946.1	Q68CZ1-1
	RPGRIP1L	ENST00000621565.5	TSL:1	c.*737T>G		3_prime_UTR	Exon 26 of 26	ENSP00000480698.1	A0A087WX34
	RPGRIP1L	ENST00000262135.9	TSL:5	c.*737T>G		3_prime_UTR	Exon 25 of 25	ENSP00000262135.4	Q68CZ1-2

Frequencies

GnomAD3 genomes AF: 0.381 AC: 57888 AN: 152032 Hom.: 12772 Cov.: 33

Gnomad AFR AF: 0.598

Gnomad AMI AF: 0.206

Gnomad AMR AF: 0.287

Gnomad ASJ AF: 0.341

Gnomad EAS AF: 0.585

Gnomad SAS AF: 0.428

Gnomad FIN AF: 0.177

Gnomad MID AF: 0.446

Gnomad NFE AF: 0.287

Gnomad OTH AF: 0.377

GnomAD4 exome AF: 0.198 AC: 25 AN: 126 Hom.: 2 Cov.: 0 AF XY: 0.183 AC XY: 15 AN XY: 82

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 0.194 AC: 21 AN: 108

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.286 AC: 4 AN: 14

Other (OTH) AF: 0.00 AC: 0 AN: 4

GnomAD4 genome AF: 0.381 AC: 57985 AN: 152148 Hom.: 12812 Cov.: 33 AF XY: 0.376 AC XY: 28004 AN XY: 74386

African (AFR) AF: 0.598 AC: 24812 AN: 41490

American (AMR) AF: 0.287 AC: 4387 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.341 AC: 1183 AN: 3472

East Asian (EAS) AF: 0.585 AC: 3032 AN: 5182

South Asian (SAS) AF: 0.428 AC: 2068 AN: 4830

European-Finnish (FIN) AF: 0.177 AC: 1880 AN: 10594

Middle Eastern (MID) AF: 0.449 AC: 132 AN: 294

European-Non Finnish (NFE) AF: 0.287 AC: 19491 AN: 67982

Other (OTH) AF: 0.385 AC: 812 AN: 2110

Alfa AF: 0.313 Hom.: 8901

Bravo AF: 0.395

Asia WGS AF: 0.509 AC: 1772 AN: 3474

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	1	Joubert syndrome 7 (1)
-	-	1	Meckel syndrome, type 5 (1)
-	-	1	Nephronophthisis 8 (1)
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.51
DANN	Benign	0.35
PhyloP100		-0.34
Mutation Taster		=100/0	polymorphism (auto)

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: rs3760008; hg19: chr16-53635251;