22-23130767-T-C

Position:

• chr22-23130767-T-C

Variant summary

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

The NM_014433.3(RSPH14):​c.421+3259A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.514 in 152,060 control chromosomes in the GnomAD database, including 20,323 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 0.51 (20323 hom., cov: 33)
• Consequence: RSPH14 NM_014433.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.189

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 (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.557 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RSPH14	NM_014433.3	c.421+3259A>G		intron_variant		ENST00000216036.9	NP_055248.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RSPH14	ENST00000216036.9	c.421+3259A>G		intron_variant		1	NM_014433.3	ENSP00000216036	P1
RSPH14	ENST00000421213.1	c.49+3259A>G		intron_variant		3		ENSP00000414155

Frequencies

GnomAD3 genomes AF: 0.514 AC: 78052 AN: 151938 Hom.: 20325 Cov.: 33

Gnomad AFR AF: 0.445

Gnomad AMI AF: 0.581

Gnomad AMR AF: 0.538

Gnomad ASJ AF: 0.556

Gnomad EAS AF: 0.392

Gnomad SAS AF: 0.438

Gnomad FIN AF: 0.514

Gnomad MID AF: 0.576

Gnomad NFE AF: 0.561

Gnomad OTH AF: 0.519

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

GnomAD4 genome AF: 0.514 AC: 78091 AN: 152060 Hom.: 20323 Cov.: 33 AF XY: 0.510 AC XY: 37926 AN XY: 74342

Gnomad4 AFR AF: 0.445

Gnomad4 AMR AF: 0.537

Gnomad4 ASJ AF: 0.556

Gnomad4 EAS AF: 0.392

Gnomad4 SAS AF: 0.438

Gnomad4 FIN AF: 0.514

Gnomad4 NFE AF: 0.561

Gnomad4 OTH AF: 0.516

Alfa AF: 0.545 Hom.: 9878

Bravo AF: 0.513

Asia WGS AF: 0.420 AC: 1462 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	1.7
DANN	Benign	0.54

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: rs9612237; hg19: chr22-23472954;