22-23069838-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_014433.3(RSPH14):c.422-5705T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.546 in 152,024 control chromosomes in the GnomAD database, including 24,121 homozygotes. 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: 𝑓 0.55 (24121 hom., cov: 33)
• Consequence: RSPH14 NM_014433.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.300

Genes affected

RSPH14 (HGNC:13437): (radial spoke head 14 homolog) This gene encodes a protein with no known function but with slight similarity to a yeast vacuolar protein. The gene is located in a region deleted in pediatric rhabdoid tumors of the brain, kidney and soft tissues, but mutations in this gene have not been associated with the disease. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (Cadd=8.812).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.658 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RSPH14	NM_014433.3	c.422-5705T>C		intron_variant		ENST00000216036.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RSPH14	ENST00000216036.9	c.422-5705T>C		intron_variant		1	NM_014433.3	P1

Frequencies

GnomAD3 genomes AF: 0.546 AC: 82934 AN: 151906 Hom.: 24116 Cov.: 33

Gnomad AFR AF: 0.336

Gnomad AMI AF: 0.554

Gnomad AMR AF: 0.574

Gnomad ASJ AF: 0.582

Gnomad EAS AF: 0.606

Gnomad SAS AF: 0.677

Gnomad FIN AF: 0.649

Gnomad MID AF: 0.532

Gnomad NFE AF: 0.635

Gnomad OTH AF: 0.579

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.546 AC: 82971 AN: 152024 Hom.: 24121 Cov.: 33 AF XY: 0.550 AC XY: 40855 AN XY: 74286

Gnomad4 AFR AF: 0.336

Gnomad4 AMR AF: 0.574

Gnomad4 ASJ AF: 0.582

Gnomad4 EAS AF: 0.607

Gnomad4 SAS AF: 0.677

Gnomad4 FIN AF: 0.649

Gnomad4 NFE AF: 0.635

Gnomad4 OTH AF: 0.580

Alfa AF: 0.610 Hom.: 46904

Bravo AF: 0.528

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
Cadd	Benign	8.8

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs3788337; hg19: -;