6-158993779-C-T

Variant names:

• chr6-158993779-C-T
• rs77876414
• NM_031924.8:c.204+60G>A

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+60G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.11 in 889,040 control chromosomes in the GnomAD database, including 10,777 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.11 (1725 hom., cov: 32)
  • Exomes 𝑓: 0.11 (9052 hom.)
• Consequence: RSPH3 NM_031924.8 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.546
• Publications: 5 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=-0.83).
• BP6: Variant 6-158993779-C-T is Benign according to our data. Variant chr6-158993779-C-T is described in ClinVar as Benign. ClinVar VariationId is 1236074.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.401 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+60G>A		intron	N/A	NP_114130.4
	RSPH3	NM_001346418.1		c.630+60G>A		intron	N/A	NP_001333347.1	Q86UC2-2
	RSPH3	NR_144434.1		n.841+60G>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+60G>A		intron	N/A	ENSP00000356036.1	A0A0C4DFU3
	RSPH3	ENST00000884885.1		c.204+60G>A		intron	N/A	ENSP00000554944.1
	RSPH3	ENST00000449822.6	TSL:2	c.204+60G>A		intron	N/A	ENSP00000393195.1	A0A0C4DG29

Frequencies

GnomAD3 genomes AF: 0.114 AC: 17346 AN: 152060 Hom.: 1714 Cov.: 32

Gnomad AFR AF: 0.0751

Gnomad AMI AF: 0.0515

Gnomad AMR AF: 0.282

Gnomad ASJ AF: 0.108

Gnomad EAS AF: 0.415

Gnomad SAS AF: 0.194

Gnomad FIN AF: 0.0914

Gnomad MID AF: 0.101

Gnomad NFE AF: 0.0758

Gnomad OTH AF: 0.125

GnomAD4 exome AF: 0.109 AC: 80567 AN: 736862 Hom.: 9052 AF XY: 0.109 AC XY: 42065 AN XY: 387554

African (AFR) AF: 0.0608 AC: 1128 AN: 18542

American (AMR) AF: 0.415 AC: 13042 AN: 31446

Ashkenazi Jewish (ASJ) AF: 0.0973 AC: 1918 AN: 19714

East Asian (EAS) AF: 0.462 AC: 15038 AN: 32518

South Asian (SAS) AF: 0.149 AC: 8199 AN: 55140

European-Finnish (FIN) AF: 0.0855 AC: 4302 AN: 50320

Middle Eastern (MID) AF: 0.101 AC: 436 AN: 4298

European-Non Finnish (NFE) AF: 0.0668 AC: 32684 AN: 489506

Other (OTH) AF: 0.108 AC: 3820 AN: 35378

GnomAD4 genome AF: 0.114 AC: 17392 AN: 152178 Hom.: 1725 Cov.: 32 AF XY: 0.120 AC XY: 8937 AN XY: 74404

African (AFR) AF: 0.0756 AC: 3138 AN: 41532

American (AMR) AF: 0.282 AC: 4313 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.108 AC: 376 AN: 3472

East Asian (EAS) AF: 0.416 AC: 2153 AN: 5180

South Asian (SAS) AF: 0.194 AC: 936 AN: 4822

European-Finnish (FIN) AF: 0.0914 AC: 967 AN: 10580

Middle Eastern (MID) AF: 0.102 AC: 30 AN: 294

European-Non Finnish (NFE) AF: 0.0758 AC: 5157 AN: 67996

Other (OTH) AF: 0.130 AC: 275 AN: 2116

Alfa AF: 0.0336 Hom.: 21

Bravo AF: 0.133

Asia WGS AF: 0.281 AC: 978 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	-0.83
CADD	Benign	0.72
DANN	Benign	0.71
PhyloP100		-0.55
Mutation Taster		=100/0	polymorphism (auto)

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: rs77876414; hg19: chr6-159414811; COSMIC: COSV51921660;