chr6-158993635-C-T

Variant names:

• chr6-158993635-C-T
• rs74640902
• NM_031924.8:c.204+204G>A

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_031924.8(RSPH3):​c.204+204G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0178 in 152,184 control chromosomes in the GnomAD database, including 33 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency: Genomes: 𝑓 0.018 (33 hom., cov: 31)
• Consequence: RSPH3 NM_031924.8 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.170
• 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=-0.89).
• BP6: Variant 6-158993635-C-T is Benign according to our data. Variant chr6-158993635-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 1316315.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.0178 (2708/152184) while in subpopulation NFE AF = 0.0237 (1611/68008). AF 95% confidence interval is 0.0227. There are 33 homozygotes in GnomAd4. There are 1289 alleles in the male GnomAd4 subpopulation. Median coverage is 31. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 33 AR,AD gene

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+204G>A		intron	N/A	NP_114130.4
	RSPH3	NM_001346418.1		c.630+204G>A		intron	N/A	NP_001333347.1	Q86UC2-2
	RSPH3	NR_144434.1		n.841+204G>A		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+204G>A		intron	N/A	ENSP00000356036.1	A0A0C4DFU3
	RSPH3	ENST00000884885.1		c.204+204G>A		intron	N/A	ENSP00000554944.1
	RSPH3	ENST00000449822.6	TSL:2	c.204+204G>A		intron	N/A	ENSP00000393195.1	A0A0C4DG29

Frequencies

GnomAD3 genomes AF: 0.0178 AC: 2706 AN: 152066 Hom.: 33 Cov.: 31

Gnomad AFR AF: 0.00923

Gnomad AMI AF: 0.0943

Gnomad AMR AF: 0.0235

Gnomad ASJ AF: 0.00662

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00871

Gnomad FIN AF: 0.0155

Gnomad MID AF: 0.0253

Gnomad NFE AF: 0.0237

Gnomad OTH AF: 0.0158

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

GnomAD4 genome AF: 0.0178 AC: 2708 AN: 152184 Hom.: 33 Cov.: 31 AF XY: 0.0173 AC XY: 1289 AN XY: 74408

African (AFR) AF: 0.00925 AC: 384 AN: 41526

American (AMR) AF: 0.0234 AC: 358 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.00662 AC: 23 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5182

South Asian (SAS) AF: 0.00872 AC: 42 AN: 4818

European-Finnish (FIN) AF: 0.0155 AC: 164 AN: 10578

Middle Eastern (MID) AF: 0.0238 AC: 7 AN: 294

European-Non Finnish (NFE) AF: 0.0237 AC: 1611 AN: 68008

Other (OTH) AF: 0.0156 AC: 33 AN: 2112

Alfa AF: 0.0196 Hom.: 5

Bravo AF: 0.0179

Asia WGS AF: 0.00491 AC: 17 AN: 3478

ClinVar

ClinVar submissions

Significance: Likely 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	-0.89
CADD	Benign	1.0
DANN	Benign	0.74
PhyloP100		-0.17
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: rs74640902; hg19: chr6-159414667;