X-18641857-TA-T

Position:

• chrX-18641857-TA-T

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_000330.4(RS1):​c.*146del variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.050 (293 hom., 1231 hem., cov: 20)
  • Exomes 𝑓: 0.14 (49 hom. 345 hem.)
• Consequence: RS1 NM_000330.4 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.54

Genes affected

RS1 (HGNC:10457): (retinoschisin 1) This gene encodes an extracellular protein that plays a crucial role in the cellular organization of the retina. The encoded protein is assembled and secreted from photoreceptors and bipolar cells as a homo-oligomeric protein complex. Mutations in this gene are responsible for X-linked retinoschisis, a common, early-onset macular degeneration in males that results in a splitting of the inner layers of the retina and severe loss in vision. [provided by RefSeq, Oct 2008]

CDKL5 (HGNC:11411): (cyclin dependent kinase like 5) This gene is a member of Ser/Thr protein kinase family and encodes a phosphorylated protein with protein kinase activity. Mutations in this gene have been associated with X-linked infantile spasm syndrome (ISSX), also known as X-linked West syndrome, and Rett syndrome (RTT). Alternate transcriptional splice variants have been characterized. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP6: Variant X-18641857-TA-T is Benign according to our data. Variant chrX-18641857-TA-T is described in ClinVar as [Benign]. Clinvar id is 1272473.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.152 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RS1	NM_000330.4	c.*146del		3_prime_UTR_variant	6/6	ENST00000379984.4	NP_000321.1
RS1	XM_047442337.1	c.*146del		3_prime_UTR_variant	4/4		XP_047298293.1
CDKL5	NM_001037343.2	c.2714-4137del		intron_variant			NP_001032420.1
CDKL5	NM_003159.3	c.2714-4137del		intron_variant			NP_003150.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RS1	ENST00000379984.4	c.*146del		3_prime_UTR_variant	6/6	1	NM_000330.4	ENSP00000369320	P1
CDKL5	ENST00000379989.6	c.2714-4137del		intron_variant		1		ENSP00000369325
CDKL5	ENST00000379996.7	c.2714-4137del		intron_variant		1		ENSP00000369332

Frequencies

GnomAD3 genomes AF: 0.0496 AC: 5188 AN: 104570 Hom.: 292 Cov.: 20 AF XY: 0.0418 AC XY: 1232 AN XY: 29500

Gnomad AFR AF: 0.157

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0157

Gnomad ASJ AF: 0.0300

Gnomad EAS AF: 0.000294

Gnomad SAS AF: 0.00481

Gnomad FIN AF: 0.00862

Gnomad MID AF: 0.0482

Gnomad NFE AF: 0.00598

Gnomad OTH AF: 0.0473

GnomAD4 exome AF: 0.145 AC: 36862 AN: 254271 Hom.: 49 Cov.: 0 AF XY: 0.00556 AC XY: 345 AN XY: 62017

Gnomad4 AFR exome AF: 0.284

Gnomad4 AMR exome AF: 0.180

Gnomad4 ASJ exome AF: 0.175

Gnomad4 EAS exome AF: 0.153

Gnomad4 SAS exome AF: 0.0977

Gnomad4 FIN exome AF: 0.148

Gnomad4 NFE exome AF: 0.138

Gnomad4 OTH exome AF: 0.163

GnomAD4 genome AF: 0.0496 AC: 5185 AN: 104574 Hom.: 293 Cov.: 20 AF XY: 0.0417 AC XY: 1231 AN XY: 29522

Gnomad4 AFR AF: 0.156

Gnomad4 AMR AF: 0.0157

Gnomad4 ASJ AF: 0.0300

Gnomad4 EAS AF: 0.000296

Gnomad4 SAS AF: 0.00526

Gnomad4 FIN AF: 0.00862

Gnomad4 NFE AF: 0.00594

Gnomad4 OTH AF: 0.0468

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Oct 05, 2019

- -

Computational scores

Source: dbNSFP v4.3

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

Publications

LitVar

Other links and lift over

dbSNP: rs377648180; hg19: chrX-18659977;