NM_031924.8:c.204+184C>G

Variant names:

• chr6-158993655-G-C
• rs80307831
• NM_031924.8:c.204+184C>G

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_031924.8(RSPH3):​c.204+184C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0168 in 151,946 control chromosomes in the GnomAD database, including 66 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.017 (66 hom., cov: 31)
• Consequence: RSPH3 NM_031924.8 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.00200
• Publications: 0 publications found

Genes affected

RSPH3 (HGNC:21054): (radial spoke head 3) The protein encoded by this gene acts as a protein kinase A anchoring protein. Mutations in this gene cause primary ciliary dyskinesia; a disorder characterized by defects of the axoneme in motile cilia and sperm flagella. The homolog of this gene was first identified in the blue-green algae Chlamydomonas as encoding a radial spoke protein that formed a structural component of motile cilia and flagella. Alternate splicing results in multiple transcript variants encoding distinct isoforms. [provided by RefSeq, Dec 2016]

TAGAP-AS1 (HGNC:55239): (TAGAP antisense RNA 1)

ACMG classification

Our verdict: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BP6: Variant 6-158993655-G-C is Benign according to our data. Variant chr6-158993655-G-C is described in ClinVar as Benign. ClinVar VariationId is 1294513.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0565 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_031924.8. 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
	RSPH3	NM_031924.8	MANE Select	c.204+184C>G		intron	N/A	NP_114130.4
	RSPH3	NM_001346418.1		c.630+184C>G		intron	N/A	NP_001333347.1	Q86UC2-2
	RSPH3	NR_144434.1		n.841+184C>G		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RSPH3	ENST00000367069.7	TSL:1 MANE Select	c.204+184C>G		intron	N/A	ENSP00000356036.1	A0A0C4DFU3
	RSPH3	ENST00000884885.1		c.204+184C>G		intron	N/A	ENSP00000554944.1
	RSPH3	ENST00000449822.6	TSL:2	c.204+184C>G		intron	N/A	ENSP00000393195.1	A0A0C4DG29

Frequencies

GnomAD3 genomes AF: 0.0168 AC: 2544 AN: 151828 Hom.: 65 Cov.: 31

Gnomad AFR AF: 0.0585

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00551

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000235

Gnomad OTH AF: 0.0129

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

GnomAD4 genome AF: 0.0168 AC: 2546 AN: 151946 Hom.: 66 Cov.: 31 AF XY: 0.0169 AC XY: 1257 AN XY: 74266

African (AFR) AF: 0.0584 AC: 2420 AN: 41404

American (AMR) AF: 0.00544 AC: 83 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3466

East Asian (EAS) AF: 0.00 AC: 0 AN: 5178

South Asian (SAS) AF: 0.00 AC: 0 AN: 4808

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10526

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000235 AC: 16 AN: 67986

Other (OTH) AF: 0.0128 AC: 27 AN: 2108

Alfa AF: 0.0158 Hom.: 13

Bravo AF: 0.0192

Asia WGS AF: 0.00375 AC: 13 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.1
DANN	Benign	0.67
PhyloP100		0.0020
Mutation Taster		=100/0	polymorphism

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: rs80307831; hg19: chr6-159414687;