X-18647213-G-T

Variant names:

• chrX-18647213-G-T
• NM_000330.4:c.304C>A

Variant summary

Our verdict is Likely benign. Variant got -1 ACMG points: 2P and 3B. PM2 BP4_Moderate BP7

The NM_000330.4(RS1):​c.304C>A​(p.Arg102Arg) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000911 in 1,097,960 control chromosomes in the GnomAD database, with no homozygous occurrence. There are no hemizygote samples in GnomAD. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 22)
  • Exomes 𝑓: 9.1e-7 (0 hom. 0 hem.)
• Consequence: RS1 NM_000330.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.00

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 Likely_benign. Variant got -1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.43).
• BP7: Synonymous conserved (PhyloP=3 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RS1	NM_000330.4	c.304C>A	p.Arg102Arg	synonymous_variant	Exon 4 of 6	ENST00000379984.4	NP_000321.1
RS1	XM_047442337.1	c.208C>A	p.Arg70Arg	synonymous_variant	Exon 2 of 4		XP_047298293.1
CDKL5	NM_001037343.2	c.2797+1123G>T		intron_variant	Intron 20 of 21		NP_001032420.1
CDKL5	NM_003159.3	c.2797+1123G>T		intron_variant	Intron 19 of 20		NP_003150.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RS1	ENST00000379984.4	c.304C>A	p.Arg102Arg	synonymous_variant	Exon 4 of 6	1	NM_000330.4	ENSP00000369320.3
CDKL5	ENST00000379989.6	c.2797+1123G>T		intron_variant	Intron 20 of 21	1		ENSP00000369325.3
CDKL5	ENST00000379996.7	c.2797+1123G>T		intron_variant	Intron 19 of 20	1		ENSP00000369332.3
RS1	ENST00000476595.1	n.795C>A		non_coding_transcript_exon_variant	Exon 3 of 5	1

Frequencies

GnomAD3 genomes Cov.: 22

GnomAD4 exome AF: 9.11e-7 AC: 1 AN: 1097960 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 363368

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000119

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 22

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.43
CADD	Benign	11
DANN	Benign	0.81

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

No publications associated with this variant yet.

Other links and lift over

hg19: chrX-18665333;