rs139625725

chr21-42482664-T-C

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_Strong BP6_Moderate BP7 BS1

The NM_080860.4(RSPH1):c.546A>G(p.Gln182=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000679 in 1,613,510 control chromosomes in the GnomAD database, including 5 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.00045 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00070 (5 hom.)
• Consequence: RSPH1 NM_080860.4 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.637

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 -11 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.73).
• BP6: Variant 21-42482664-T-C is Benign according to our data. Variant chr21-42482664-T-C is described in ClinVar as [Benign]. Clinvar id is 414805.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=0.637 with no splicing effect.
• BS1: Variant frequency is greater than expected in population sas. gnomad4_exome allele frequency = 0.000702 (1026/1461158) while in subpopulation SAS AF= 0.00483 (416/86114). AF 95% confidence interval is 0.00445. There are 5 homozygotes in gnomad4_exome. There are 637 alleles in male gnomad4_exome subpopulation. Median coverage is 29. This position pass quality control queck.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RSPH1	NM_080860.4	c.546A>G	p.Gln182=	synonymous_variant	6/9	ENST00000291536.8
RSPH1	NM_001286506.2	c.432A>G	p.Gln144=	synonymous_variant	5/8
RSPH1	XM_005261208.3	c.339A>G	p.Gln113=	synonymous_variant	4/7
RSPH1	XM_011529786.2	c.501+3005A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RSPH1	ENST00000291536.8	c.546A>G	p.Gln182=	synonymous_variant	6/9	1	NM_080860.4	P1
RSPH1	ENST00000398352.3	c.432A>G	p.Gln144=	synonymous_variant	5/8	5
RSPH1	ENST00000493019.1	n.2164A>G		non_coding_transcript_exon_variant	5/8	2

Frequencies

GnomAD3 genomes AF: 0.000453 AC: 69 AN: 152234 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000482

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000262

Gnomad ASJ AF: 0.00375

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00248

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.000529

Gnomad OTH AF: 0.000478

GnomAD3 exomes AF: 0.00106 AC: 267 AN: 250936 Hom.: 1 AF XY: 0.00133 AC XY: 180 AN XY: 135672

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000670

Gnomad ASJ exome AF: 0.00357

Gnomad EAS exome AF: 0.0000544

Gnomad SAS exome AF: 0.00443

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000616

Gnomad OTH exome AF: 0.000326

GnomAD4 exome AF: 0.000702 AC: 1026 AN: 1461158 Hom.: 5 Cov.: 29 AF XY: 0.000876 AC XY: 637 AN XY: 726938

Gnomad4 AFR exome AF: 0.0000598

Gnomad4 AMR exome AF: 0.000674

Gnomad4 ASJ exome AF: 0.00364

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00483

Gnomad4 FIN exome AF: 0.0000187

Gnomad4 NFE exome AF: 0.000360

Gnomad4 OTH exome AF: 0.00109

GnomAD4 genome AF: 0.000453 AC: 69 AN: 152352 Hom.: 0 Cov.: 32 AF XY: 0.000564 AC XY: 42 AN XY: 74506

Gnomad4 AFR AF: 0.0000481

Gnomad4 AMR AF: 0.000261

Gnomad4 ASJ AF: 0.00375

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00249

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000529

Gnomad4 OTH AF: 0.000473

Alfa AF: 0.000762 Hom.: 0

Bravo AF: 0.000468

Asia WGS AF: 0.00173 AC: 6 AN: 3478

EpiCase AF: 0.00131

EpiControl AF: 0.000948

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Primary ciliary dyskinesia Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jan 01, 2024

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.73
Cadd	Benign	2.1
Dann	Benign	0.44

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: rs139625725; hg19: chr21-43902774;