21-42472765-G-A

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_080860.4(RSPH1):c.*53C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0909 in 1,405,072 control chromosomes in the GnomAD database, including 6,873 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.074 (615 hom., cov: 33)
  • Exomes 𝑓: 0.093 (6258 hom.)
• Consequence: RSPH1 NM_080860.4 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.124

Genes affected

RSPH1 (HGNC:12371): (radial spoke head component 1) This gene encodes a male meiotic metaphase chromosome-associated acidic protein. This gene is expressed in tissues with motile cilia or flagella, including the trachea, lungs, airway brushings, and testes. Mutations in this gene result in primary ciliary dyskinesia-24. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Sep 2014]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BP6: Variant 21-42472765-G-A is Benign according to our data. Variant chr21-42472765-G-A is described in ClinVar as [Benign]. Clinvar id is 1283939.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.147 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RSPH1	NM_080860.4	c.*53C>T		3_prime_UTR_variant	9/9	ENST00000291536.8
RSPH1	NM_001286506.2	c.*53C>T		3_prime_UTR_variant	8/8
RSPH1	XM_005261208.3	c.*53C>T		3_prime_UTR_variant	7/7
RSPH1	XM_011529786.2	c.*53C>T		3_prime_UTR_variant	8/8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RSPH1	ENST00000291536.8	c.*53C>T		3_prime_UTR_variant	9/9	1	NM_080860.4	P1
RSPH1	ENST00000398352.3	c.*53C>T		3_prime_UTR_variant	8/8	5
RSPH1	ENST00000493019.1	n.2601C>T		non_coding_transcript_exon_variant	8/8	2

Frequencies

GnomAD3 genomes AF: 0.0738 AC: 11222 AN: 152000 Hom.: 613 Cov.: 33

Gnomad AFR AF: 0.0200

Gnomad AMI AF: 0.156

Gnomad AMR AF: 0.0869

Gnomad ASJ AF: 0.129

Gnomad EAS AF: 0.0608

Gnomad SAS AF: 0.156

Gnomad FIN AF: 0.0784

Gnomad MID AF: 0.184

Gnomad NFE AF: 0.0933

Gnomad OTH AF: 0.0876

GnomAD4 exome AF: 0.0930 AC: 116536 AN: 1252954 Hom.: 6258 Cov.: 17 AF XY: 0.0966 AC XY: 61254 AN XY: 634348

Gnomad4 AFR exome AF: 0.0189

Gnomad4 AMR exome AF: 0.0761

Gnomad4 ASJ exome AF: 0.124

Gnomad4 EAS exome AF: 0.0776

Gnomad4 SAS exome AF: 0.164

Gnomad4 FIN exome AF: 0.0752

Gnomad4 NFE exome AF: 0.0900

Gnomad4 OTH exome AF: 0.0963

GnomAD4 genome AF: 0.0738 AC: 11233 AN: 152118 Hom.: 615 Cov.: 33 AF XY: 0.0749 AC XY: 5570 AN XY: 74374

Gnomad4 AFR AF: 0.0199

Gnomad4 AMR AF: 0.0871

Gnomad4 ASJ AF: 0.129

Gnomad4 EAS AF: 0.0609

Gnomad4 SAS AF: 0.156

Gnomad4 FIN AF: 0.0784

Gnomad4 NFE AF: 0.0933

Gnomad4 OTH AF: 0.0938

Alfa AF: 0.0818 Hom.: 424

Bravo AF: 0.0723

Asia WGS AF: 0.122 AC: 423 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Feb 05, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
Cadd	Benign	3.0
Dann	Benign	0.37

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs1043807; hg19: chr21-43892875;