NM_014433.3:c.422-5705T>C

Variant names:

• chr22-23069838-A-G
• rs3788337
• NM_014433.3:c.422-5705T>C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 22 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 (Cadd=8.812).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.658 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RSPH14	NM_014433.3	MANE Select	c.422-5705T>C		intron	N/A	NP_055248.1	Q9UHP6

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RSPH14	ENST00000216036.9	TSL:1 MANE Select	c.422-5705T>C		intron	N/A	ENSP00000216036.4	Q9UHP6

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

African (AFR) AF: 0.336 AC: 13912 AN: 41458

American (AMR) AF: 0.574 AC: 8776 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.582 AC: 2020 AN: 3472

East Asian (EAS) AF: 0.607 AC: 3114 AN: 5134

South Asian (SAS) AF: 0.677 AC: 3269 AN: 4826

European-Finnish (FIN) AF: 0.649 AC: 6856 AN: 10564

Middle Eastern (MID) AF: 0.541 AC: 159 AN: 294

European-Non Finnish (NFE) AF: 0.635 AC: 43138 AN: 67970

Other (OTH) AF: 0.580 AC: 1222 AN: 2108

Alfa AF: 0.602 Hom.: 99107

Bravo AF: 0.528

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
CADD	Benign	8.8
PhyloP100		-0.30

Splicing

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

Other links and lift over

dbSNP: rs3788337;