6-158999513-G-C

Variant names:

• chr6-158999513-G-C
• rs61750776
• NM_031924.8:c.38C>G

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_031924.8(RSPH3):​c.38C>G​(p.Pro13Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00831 in 1,566,622 control chromosomes in the GnomAD database, including 946 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.044 (476 hom., cov: 32)
  • Exomes 𝑓: 0.0045 (470 hom.)
• Consequence: RSPH3 NM_031924.8 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 1.35
• Publications: 3 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0015439689).
• BP6: Variant 6-158999513-G-C is Benign according to our data. Variant chr6-158999513-G-C is described in ClinVar as Benign. ClinVar VariationId is 475833.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.15 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RSPH3	NM_031924.8	c.38C>G	p.Pro13Arg	missense_variant	Exon 1 of 8	ENST00000367069.7	NP_114130.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RSPH3	ENST00000367069.7	c.38C>G	p.Pro13Arg	missense_variant	Exon 1 of 8	1	NM_031924.8	ENSP00000356036.1

Frequencies

GnomAD3 genomes AF: 0.0440 AC: 6687 AN: 152054 Hom.: 475 Cov.: 32

Gnomad AFR AF: 0.153

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0154

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0127

Gnomad NFE AF: 0.000573

Gnomad OTH AF: 0.0398

GnomAD2 exomes AF: 0.0128 AC: 2835 AN: 222098 AF XY: 0.00938

Gnomad AFR exome AF: 0.159

Gnomad AMR exome AF: 0.00742

Gnomad ASJ exome AF: 0.000279

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000406

Gnomad OTH exome AF: 0.00534

GnomAD4 exome AF: 0.00447 AC: 6329 AN: 1414450 Hom.: 470 Cov.: 31 AF XY: 0.00386 AC XY: 2689 AN XY: 696982

African (AFR) AF: 0.158 AC: 5109 AN: 32310

American (AMR) AF: 0.00889 AC: 362 AN: 40712

Ashkenazi Jewish (ASJ) AF: 0.000428 AC: 10 AN: 23360

East Asian (EAS) AF: 0.00 AC: 0 AN: 39030

South Asian (SAS) AF: 0.000285 AC: 23 AN: 80686

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 50796

Middle Eastern (MID) AF: 0.0111 AC: 60 AN: 5414

European-Non Finnish (NFE) AF: 0.000192 AC: 208 AN: 1083886

Other (OTH) AF: 0.00956 AC: 557 AN: 58256

GnomAD4 genome AF: 0.0440 AC: 6694 AN: 152172 Hom.: 476 Cov.: 32 AF XY: 0.0430 AC XY: 3201 AN XY: 74400

African (AFR) AF: 0.153 AC: 6335 AN: 41466

American (AMR) AF: 0.0154 AC: 235 AN: 15296

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 5174

South Asian (SAS) AF: 0.00 AC: 0 AN: 4816

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10620

Middle Eastern (MID) AF: 0.0102 AC: 3 AN: 294

European-Non Finnish (NFE) AF: 0.000573 AC: 39 AN: 68016

Other (OTH) AF: 0.0389 AC: 82 AN: 2108

Alfa AF: 0.00279 Hom.: 4

Bravo AF: 0.0507

ESP6500AA AF: 0.155 AC: 685

ESP6500EA AF: 0.000814 AC: 7

ExAC AF: 0.0144 AC: 1748

Asia WGS AF: 0.00924 AC: 32 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Primary ciliary dyskinesia 32 Benign:1

Feb 02, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

not provided Benign:1

Sep 07, 2019

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.70	T
BayesDel_noAF	Benign	-0.63
CADD	Benign	14
DANN	Benign	0.91
DEOGEN2	Benign	0.026	T;.;T
Eigen	Benign	-0.91
Eigen_PC	Benign	-0.84
FATHMM_MKL	Benign	0.077	N
LIST_S2	Benign	0.68	T;T;T
MetaRNN	Benign	0.0015	T;T;T
MetaSVM	Benign	-0.94	T
MutationAssessor	Benign	0.0	.;.;N
PhyloP100		1.4
PrimateAI	Benign	0.29	T
PROVEAN	Benign	-1.5	N;N;N
REVEL	Benign	0.059
Sift	Benign	0.11	T;T;T
Sift4G	Benign	0.52	T;T;T
Vest4		0.063
ClinPred		0.016	T
GERP RS		-0.22
PromoterAI		0.073	Neutral
Varity_R		0.031
gMVP		0.041
Mutation Taster		=99/1	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: rs61750776; hg19: chr6-159420545;