22-23130767-T-C

Variant names:

• chr22-23130767-T-C
• rs9612237
• NM_014433.3:c.421+3259A>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 5 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014433.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RSPH14	NM_014433.3	MANE Select	c.421+3259A>G		intron	N/A	NP_055248.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RSPH14	ENST00000216036.9	TSL:1 MANE Select	c.421+3259A>G		intron	N/A	ENSP00000216036.4
	RSPH14	ENST00000421213.1	TSL:3	c.49+3259A>G		intron	N/A	ENSP00000414155.1

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

African (AFR) AF: 0.445 AC: 18448 AN: 41476

American (AMR) AF: 0.537 AC: 8218 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.556 AC: 1928 AN: 3470

East Asian (EAS) AF: 0.392 AC: 2022 AN: 5160

South Asian (SAS) AF: 0.438 AC: 2112 AN: 4824

European-Finnish (FIN) AF: 0.514 AC: 5431 AN: 10564

Middle Eastern (MID) AF: 0.578 AC: 170 AN: 294

European-Non Finnish (NFE) AF: 0.561 AC: 38141 AN: 67950

Other (OTH) AF: 0.516 AC: 1091 AN: 2114

Alfa AF: 0.545 Hom.: 11131

Bravo AF: 0.513

Asia WGS AF: 0.420 AC: 1462 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	1.7
DANN	Benign	0.54
PhyloP100		-0.19
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: rs9612237; hg19: chr22-23472954;