Variant 6-158993867-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_031924.8(RSPH3):c.176A>G(p.Asn59Ser) variant causes a missense change. The variant allele was found at a frequency of 0.106 in 1,607,238 control chromosomes in the GnomAD database, including 16,796 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Synonymous variant affecting the same amino acid position (i.e. N59N) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.11 ( 1722 hom., cov: 32)

Exomes 𝑓: 0.11 ( 15074 hom. )

Consequence

RSPH3
NM_031924.8 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 6.01

Variant links:

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]

RSPH3 links:

TAGAP-AS1 (HGNC:55239): (TAGAP antisense RNA 1)

TAGAP-AS1 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.001992017).

BP6

Variant 6-158993867-T-C is Benign according to our data. Variant chr6-158993867-T-C is described in ClinVar as [Benign]. Clinvar id is 1166975.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.4 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RSPH3	NM_031924.8 linkuse as main transcript	c.176A>G	p.Asn59Ser	missense_variant	2/8	ENST00000367069.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris
RSPH3	ENST00000367069.7 linkuse as main transcript	c.176A>G	p.Asn59Ser	missense_variant	2/8	1	NM_031924.8	P1
RSPH3	ENST00000449822.5 linkuse as main transcript	c.176A>G	p.Asn59Ser	missense_variant	2/6	2
TAGAP-AS1	ENST00000607391.5 linkuse as main transcript	n.236+3295T>C		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes

AF:

0.114

AC:

17332

AN:

152046

Hom.:

1711

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0751

Gnomad AMI

AF:

0.0516

Gnomad AMR

AF:

0.282

Gnomad ASJ

AF:

0.108

Gnomad EAS

AF:

0.414

Gnomad SAS

AF:

0.194

Gnomad FIN

AF:

0.0913

Gnomad MID

AF:

0.101

Gnomad NFE

AF:

0.0758

Gnomad OTH

AF:

0.125

GnomAD3 exomes

AF:

0.171

AC:

42919

AN:

251060

Hom.:

6854

AF XY:

0.159

AC XY:

21644

AN XY:

135712

show subpopulations

Gnomad AFR exome

AF:

0.0714

Gnomad AMR exome

AF:

0.473

Gnomad ASJ exome

AF:

0.106

Gnomad EAS exome

AF:

0.401

Gnomad SAS exome

AF:

0.175

Gnomad FIN exome

AF:

0.0861

Gnomad NFE exome

AF:

0.0786

Gnomad OTH exome

AF:

0.145

GnomAD4 exome

AF:

0.106

AC:

153767

AN:

1455074

Hom.:

15074

Cov.:

AF XY:

0.106

AC XY:

76979

AN XY:

724280

show subpopulations

Gnomad4 AFR exome

AF:

0.0679

Gnomad4 AMR exome

AF:

0.455

Gnomad4 ASJ exome

AF:

0.106

Gnomad4 EAS exome

AF:

0.462

Gnomad4 SAS exome

AF:

0.172

Gnomad4 FIN exome

AF:

0.0885

Gnomad4 NFE exome

AF:

0.0751

Gnomad4 OTH exome

AF:

0.115

GnomAD4 genome

AF:

0.114

AC:

17379

AN:

152164

Hom.:

1722

Cov.:

AF XY:

0.120

AC XY:

8914

AN XY:

74384

show subpopulations

Gnomad4 AFR

AF:

0.0756

Gnomad4 AMR

AF:

0.283

Gnomad4 ASJ

AF:

0.108

Gnomad4 EAS

AF:

0.415

Gnomad4 SAS

AF:

0.194

Gnomad4 FIN

AF:

0.0913

Gnomad4 NFE

AF:

0.0758

Gnomad4 OTH

AF:

0.130

Alfa

AF:

0.0943

Hom.:

2075

Bravo

AF:

0.133

TwinsUK

AF:

0.0734

AC:

272

ALSPAC

AF:

0.0807

AC:

311

ESP6500AA

AF:

0.0803

AC:

354

ESP6500EA

AF:

0.0831

AC:

715

ExAC

AF:

0.159

AC:

19278

Asia WGS

AF:

0.283

AC:

982

AN:

3478

EpiCase

AF:

0.0764

EpiControl

AF:

0.0809

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Primary ciliary dyskinesia 32

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 31, 2024

- -

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Feb 25, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.23

BayesDel_addAF

Benign

-0.60

BayesDel_noAF

Benign

-0.50

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.11

T;.;T

Eigen

Uncertain

0.43

Eigen_PC

Uncertain

0.45

FATHMM_MKL

Uncertain

0.95

LIST_S2

Uncertain

0.89

D;T;D

MetaRNN

Benign

0.0020

T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.9

.;.;L

MutationTaster

Benign

0.00035

P;P;P;P

PrimateAI

Uncertain

0.61

PROVEAN

Uncertain

-4.3

D;D;D

REVEL

Benign

0.19

Sift

Benign

0.30

T;T;T

Sift4G

Benign

0.21

T;T;T

Polyphen

0.99

.;.;D

Vest4

0.25

MPC

0.79

ClinPred

0.050

GERP RS

5.7

Varity_R

0.30

gMVP

0.28

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over