rs60476423

Variant names:

• chr14-67727376-G-C
• rs60476423
• NM_152443.3:c.658+186G>C

Your query was ambiguous. Multiple possible variants found:

• chr14-67727376-G-C
• chr14-67727376-G-T

Variant summary

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

The NM_152443.3(RDH12):​c.658+186G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0908 in 615,380 control chromosomes in the GnomAD database, including 2,740 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.090 (629 hom., cov: 32)
  • Exomes 𝑓: 0.091 (2111 hom.)
• Consequence: RDH12 NM_152443.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.252
• Publications: 0 publications found

Genes affected

RDH12 (HGNC:19977): (retinol dehydrogenase 12) The protein encoded by this gene is an NADPH-dependent retinal reductase whose highest activity is toward 9-cis and all-trans-retinol. The encoded enzyme also plays a role in the metabolism of short-chain aldehydes but does not exhibit steroid dehydrogenase activity. Defects in this gene are a cause of Leber congenital amaurosis type 13 and Retinitis Pigmentosa 53. [provided by RefSeq, Sep 2015]

GPHN (HGNC:15465): (gephyrin) This gene encodes a neuronal assembly protein that anchors inhibitory neurotransmitter receptors to the postsynaptic cytoskeleton via high affinity binding to a receptor subunit domain and tubulin dimers. In nonneuronal tissues, the encoded protein is also required for molybdenum cofactor biosynthesis. Mutations in this gene may be associated with the neurological condition hyperplexia and also lead to molybdenum cofactor deficiency. Numerous alternatively spliced transcript variants encoding different isoforms have been described; however, the full-length nature of all transcript variants is not currently known. [provided by RefSeq, Jul 2008]

ZFYVE26 (HGNC:20761): (zinc finger FYVE-type containing 26) This gene encodes a protein which contains a FYVE zinc finger binding domain. The presence of this domain is thought to target these proteins to membrane lipids through interaction with phospholipids in the membrane. Mutations in this gene are associated with autosomal recessive spastic paraplegia-15. [provided by RefSeq, Oct 2008]

ZFYVE26 Gene-Disease associations (from GenCC):

• hereditary spastic paraplegia 15

  Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), G2P, Orphanet, Myriad Women’s Health

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BP6: Variant 14-67727376-G-C is Benign according to our data. Variant chr14-67727376-G-C is described in ClinVar as Benign. ClinVar VariationId is 1257532.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.105 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_152443.3. 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
	RDH12	NM_152443.3	MANE Select	c.658+186G>C		intron	N/A	NP_689656.2	A0A0S2Z613

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RDH12	ENST00000551171.6	TSL:1 MANE Select	c.658+186G>C		intron	N/A	ENSP00000449079.1	Q96NR8
	RDH12	ENST00000267502.3	TSL:5	c.658+186G>C		intron	N/A	ENSP00000267502.3	Q96NR8
	ZFYVE26	ENST00000394455.6	TSL:2	n.4132C>G		splice_region non_coding_transcript_exon	Exon 15 of 15

Frequencies

GnomAD3 genomes AF: 0.0896 AC: 13619 AN: 151976 Hom.: 627 Cov.: 32

Gnomad AFR AF: 0.0953

Gnomad AMI AF: 0.00877

Gnomad AMR AF: 0.0938

Gnomad ASJ AF: 0.0992

Gnomad EAS AF: 0.00501

Gnomad SAS AF: 0.112

Gnomad FIN AF: 0.119

Gnomad MID AF: 0.203

Gnomad NFE AF: 0.0847

Gnomad OTH AF: 0.119

GnomAD4 exome AF: 0.0912 AC: 42265 AN: 463288 Hom.: 2111 Cov.: 4 AF XY: 0.0933 AC XY: 23012 AN XY: 246752

African (AFR) AF: 0.102 AC: 1328 AN: 12994

American (AMR) AF: 0.0953 AC: 2202 AN: 23102

Ashkenazi Jewish (ASJ) AF: 0.105 AC: 1559 AN: 14822

East Asian (EAS) AF: 0.00273 AC: 82 AN: 30036

South Asian (SAS) AF: 0.115 AC: 5549 AN: 48248

European-Finnish (FIN) AF: 0.129 AC: 3687 AN: 28482

Middle Eastern (MID) AF: 0.180 AC: 361 AN: 2010

European-Non Finnish (NFE) AF: 0.0897 AC: 24865 AN: 277324

Other (OTH) AF: 0.100 AC: 2632 AN: 26270

GnomAD4 genome AF: 0.0896 AC: 13623 AN: 152092 Hom.: 629 Cov.: 32 AF XY: 0.0913 AC XY: 6786 AN XY: 74362

African (AFR) AF: 0.0951 AC: 3947 AN: 41482

American (AMR) AF: 0.0938 AC: 1433 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.0992 AC: 344 AN: 3468

East Asian (EAS) AF: 0.00502 AC: 26 AN: 5182

South Asian (SAS) AF: 0.113 AC: 542 AN: 4810

European-Finnish (FIN) AF: 0.119 AC: 1254 AN: 10560

Middle Eastern (MID) AF: 0.204 AC: 60 AN: 294

European-Non Finnish (NFE) AF: 0.0847 AC: 5761 AN: 67998

Other (OTH) AF: 0.118 AC: 248 AN: 2110

Alfa AF: 0.0893 Hom.: 89

Bravo AF: 0.0870

Asia WGS AF: 0.0590 AC: 205 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	1.6
DANN	Benign	0.77
PhyloP100		-0.25
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: rs60476423; hg19: chr14-68194093;