chr8-10606565-A-C

Variant names:

• chr8-10606565-A-C
• rs60196627
• NM_178857.6:c.*330T>G

Variant summary

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

The NM_178857.6(RP1L1):​c.*330T>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 0.143 in 326,108 control chromosomes in the GnomAD database, including 4,178 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.15 (2025 hom., cov: 34)
  • Exomes 𝑓: 0.14 (2153 hom.)
• Consequence: RP1L1 NM_178857.6 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.626
• Publications: 4 publications found

Genes affected

RP1L1 (HGNC:15946): (RP1 like 1) This gene encodes a member of the doublecortin family. The protein encoded by this gene contains two N-terminal doublecortin domains, which bind microtubules and regulate microtubule polymerization, and two C-terminal large repetitive regions, both of which contain a high percentage of glutamine and glutamic acid residues. This protein is a retinal-specific protein. Its exact length varies among individuals due to the presence of a 16aa repeat in the first C-terminal repetitive region. The 16aa repeat is encoded by the highly polymorphic 48-bp repeat, and 1-6 copies of the 16aa repeat have been identified in normal individuals. The current reference sequence shown here has a single copy of the 16aa repeat. This protein and the RP1 protein, another retinal-specific protein, play essential and synergistic roles in affecting photosensitivity and outer segment morphogenesis of rod photoreceptors. Mutations in this gene cause occult macular dystrophy (OMD). [provided by RefSeq, Sep 2010]

RP1L1 Gene-Disease associations (from GenCC):

• occult macular dystrophy

  Inheritance: AD Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Laboratory for Molecular Medicine, Orphanet, G2P, Labcorp Genetics (formerly Invitae), Ambry Genetics
• retinitis pigmentosa

  Inheritance: AD, AR Classification: DEFINITIVE, SUPPORTIVE Submitted by: Orphanet, G2P
• retinitis pigmentosa 88

  Inheritance: AR, SD Classification: STRONG, LIMITED Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae), PanelApp Australia
• cone dystrophy

  Inheritance: AR Classification: LIMITED Submitted by: G2P

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BP6: Variant 8-10606565-A-C is Benign according to our data. Variant chr8-10606565-A-C is described in ClinVar as Benign. ClinVar VariationId is 361191.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.396 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_178857.6. 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
	RP1L1	NM_178857.6	MANE Select	c.*330T>G		3_prime_UTR	Exon 4 of 4	NP_849188.4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RP1L1	ENST00000382483.4	TSL:1 MANE Select	c.*330T>G		3_prime_UTR	Exon 4 of 4	ENSP00000371923.3	Q8IWN7-1

Frequencies

GnomAD3 genomes AF: 0.150 AC: 22853 AN: 152088 Hom.: 2015 Cov.: 34

Gnomad AFR AF: 0.173

Gnomad AMI AF: 0.130

Gnomad AMR AF: 0.171

Gnomad ASJ AF: 0.121

Gnomad EAS AF: 0.411

Gnomad SAS AF: 0.114

Gnomad FIN AF: 0.0660

Gnomad MID AF: 0.149

Gnomad NFE AF: 0.130

Gnomad OTH AF: 0.148

GnomAD4 exome AF: 0.137 AC: 23797 AN: 173902 Hom.: 2153 Cov.: 2 AF XY: 0.136 AC XY: 12385 AN XY: 91378

African (AFR) AF: 0.174 AC: 847 AN: 4854

American (AMR) AF: 0.148 AC: 884 AN: 5982

Ashkenazi Jewish (ASJ) AF: 0.106 AC: 559 AN: 5294

East Asian (EAS) AF: 0.390 AC: 3469 AN: 8898

South Asian (SAS) AF: 0.114 AC: 2428 AN: 21252

European-Finnish (FIN) AF: 0.0690 AC: 599 AN: 8680

Middle Eastern (MID) AF: 0.139 AC: 105 AN: 756

European-Non Finnish (NFE) AF: 0.125 AC: 13597 AN: 108450

Other (OTH) AF: 0.134 AC: 1309 AN: 9736

GnomAD4 genome AF: 0.150 AC: 22894 AN: 152206 Hom.: 2025 Cov.: 34 AF XY: 0.148 AC XY: 10991 AN XY: 74432

African (AFR) AF: 0.173 AC: 7169 AN: 41526

American (AMR) AF: 0.171 AC: 2612 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.121 AC: 419 AN: 3470

East Asian (EAS) AF: 0.411 AC: 2115 AN: 5150

South Asian (SAS) AF: 0.114 AC: 548 AN: 4824

European-Finnish (FIN) AF: 0.0660 AC: 700 AN: 10614

Middle Eastern (MID) AF: 0.150 AC: 44 AN: 294

European-Non Finnish (NFE) AF: 0.130 AC: 8834 AN: 68000

Other (OTH) AF: 0.158 AC: 334 AN: 2114

Alfa AF: 0.151 Hom.: 818

Bravo AF: 0.160

Asia WGS AF: 0.269 AC: 934 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)
-	-	1	Occult macular dystrophy (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.32
DANN	Benign	0.42
PhyloP100		-0.63
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: rs60196627; hg19: chr8-10464075;