rs116017511

Variant names:

• chr6-158993902-T-C
• rs116017511
• NM_031924.8:c.141A>G

Your query was ambiguous. Multiple possible variants found:

• chr6-158993902-T-C
• chr6-158993902-T-G

Variant summary

Our verdict is Benign. The variant received -15 ACMG points: 0P and 15B. BP4_Strong BP6_Moderate BP7 BS1 BS2

The NM_031924.8(RSPH3):​c.141A>G​(p.Gly47Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00127 in 1,608,162 control chromosomes in the GnomAD database, including 24 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0064 (9 hom., cov: 32)
  • Exomes 𝑓: 0.00074 (15 hom.)
• Consequence: RSPH3 NM_031924.8 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.00500
• Publications: 1 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 -15 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.54).
• BP6: Variant 6-158993902-T-C is Benign according to our data. Variant chr6-158993902-T-C is described in ClinVar as Benign. ClinVar VariationId is 475834.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=0.005 with no splicing effect.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00636 (968/152286) while in subpopulation AFR AF = 0.0221 (917/41550). AF 95% confidence interval is 0.0209. There are 9 homozygotes in GnomAd4. There are 456 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 9 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.141A>G	p.Gly47Gly	synonymous	Exon 2 of 8	NP_114130.4
	RSPH3	NM_001346418.1		c.567A>G	p.Gly189Gly	synonymous	Exon 2 of 6	NP_001333347.1	Q86UC2-2
	RSPH3	NR_144434.1		n.778A>G		non_coding_transcript_exon	Exon 2 of 9

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RSPH3	ENST00000367069.7	TSL:1 MANE Select	c.141A>G	p.Gly47Gly	synonymous	Exon 2 of 8	ENSP00000356036.1	A0A0C4DFU3
	RSPH3	ENST00000884885.1		c.141A>G	p.Gly47Gly	synonymous	Exon 2 of 7	ENSP00000554944.1
	RSPH3	ENST00000449822.6	TSL:2	c.141A>G	p.Gly47Gly	synonymous	Exon 2 of 6	ENSP00000393195.1	A0A0C4DG29

Frequencies

GnomAD3 genomes AF: 0.00635 AC: 966 AN: 152168 Hom.: 9 Cov.: 32

Gnomad AFR AF: 0.0221

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00190

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: 0.000206

Gnomad OTH AF: 0.00382

GnomAD2 exomes AF: 0.00173 AC: 435 AN: 251308 AF XY: 0.00123

Gnomad AFR exome AF: 0.0228

Gnomad AMR exome AF: 0.00110

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000194

Gnomad OTH exome AF: 0.000815

GnomAD4 exome AF: 0.000740 AC: 1077 AN: 1455876 Hom.: 15 Cov.: 28 AF XY: 0.000644 AC XY: 467 AN XY: 724614

African (AFR) AF: 0.0224 AC: 746 AN: 33352

American (AMR) AF: 0.00130 AC: 58 AN: 44684

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26078

East Asian (EAS) AF: 0.00 AC: 0 AN: 39616

South Asian (SAS) AF: 0.0000116 AC: 1 AN: 86078

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53370

Middle Eastern (MID) AF: 0.00139 AC: 8 AN: 5756

European-Non Finnish (NFE) AF: 0.000153 AC: 169 AN: 1106742

Other (OTH) AF: 0.00158 AC: 95 AN: 60200

GnomAD4 genome AF: 0.00636 AC: 968 AN: 152286 Hom.: 9 Cov.: 32 AF XY: 0.00612 AC XY: 456 AN XY: 74470

African (AFR) AF: 0.0221 AC: 917 AN: 41550

American (AMR) AF: 0.00190 AC: 29 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5188

South Asian (SAS) AF: 0.00 AC: 0 AN: 4828

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10618

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

European-Non Finnish (NFE) AF: 0.000206 AC: 14 AN: 68020

Other (OTH) AF: 0.00378 AC: 8 AN: 2114

Alfa AF: 0.00304 Hom.: 5

Bravo AF: 0.00700

Asia WGS AF: 0.000289 AC: 1 AN: 3478

EpiCase AF: 0.0000545

EpiControl AF: 0.000356

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	Primary ciliary dyskinesia 32 (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.54
CADD	Benign	7.0
DANN	Benign	0.70
PhyloP100		0.0050
Mutation Taster		=97/3	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs116017511; hg19: chr6-159414934;