chr6-158993635-C-T

Position:

• chr6-158993635-C-T

Variant summary

Our verdict is Benign. Variant got -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

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

Verdict is Benign. Variant got -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 id 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 male gnomad4 subpopulation. Median coverage is 31. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 33 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RSPH3	NM_031924.8	c.204+204G>A		intron_variant		ENST00000367069.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RSPH3	ENST00000367069.7	c.204+204G>A		intron_variant		1	NM_031924.8	P1
RSPH3	ENST00000449822.5	c.204+204G>A		intron_variant		2
TAGAP-AS1	ENST00000607391.5	n.236+3063C>T		intron_variant, non_coding_transcript_variant		3

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

Gnomad4 AFR AF: 0.00925

Gnomad4 AMR AF: 0.0234

Gnomad4 ASJ AF: 0.00662

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00872

Gnomad4 FIN AF: 0.0155

Gnomad4 NFE AF: 0.0237

Gnomad4 OTH AF: 0.0156

Alfa AF: 0.0199 Hom.: 5

Bravo AF: 0.0179

Asia WGS AF: 0.00491 AC: 17 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely 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	-0.89
CADD	Benign	1.0
DANN	Benign	0.74

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: rs74640902; hg19: chr6-159414667;