Variant rs759434603 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_030785.4(RSPH6A):c.1538G>T(p.Gly513Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,868 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

RSPH6A
NM_030785.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.764

Variant links:

Genes affected

RSPH6A (HGNC:14241): (radial spoke head 6 homolog A) The protein encoded by this gene is similar to a sea urchin radial spoke head protein. Radial spoke protein complexes form part of the axoneme of eukaryotic flagella and are located between the axoneme's outer ring of doublet microtubules and central pair of microtubules. In Chlamydomonas, radial spoke proteins are thought to regulate the activity of dynein and the symmetry of flagellar bending patterns. This gene maps to a region of chromosome 19 that is linked to primary ciliary dyskinesia-2 (CILD2). [provided by RefSeq, Jul 2008]

RSPH6A links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.117422014).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RSPH6A	NM_030785.4 link	c.1538G>T	p.Gly513Val	missense_variant	Exon 3 of 6	ENST00000221538.8	NP_110412.1	Q9H0K4
RSPH6A	XM_011527351.3 link	c.1538G>T	p.Gly513Val	missense_variant	Exon 3 of 6		XP_011525653.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
RSPH6A	ENST00000221538.8 link	c.1538G>T	p.Gly513Val	missense_variant	Exon 3 of 6	1	NM_030785.4	ENSP00000221538.2	Q9H0K4
RSPH6A	ENST00000597055.1 link	c.1538G>T	p.Gly513Val	missense_variant	Exon 3 of 6	1		ENSP00000472630.1	M0R2K1
RSPH6A	ENST00000600188.5 link	c.746G>T	p.Gly249Val	missense_variant	Exon 2 of 5	2		ENSP00000471559.1	M0R103

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000796

AC:

AN:

251256

Hom.:

AF XY:

0.0000147

AC XY:

AN XY:

135830

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000176

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461868

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

727234

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

8.99e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ExAC

AF:

0.0000165

AC:

EpiCase

AF:

0.00

EpiControl

AF:

0.000119

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.24

BayesDel_addAF

Benign

-0.24

BayesDel_noAF

Benign

-0.56

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.026

T;.;T

Eigen

Benign

-0.24

Eigen_PC

Benign

-0.37

FATHMM_MKL

Benign

0.28

LIST_S2

Benign

0.26

T;T;T

M_CAP

Benign

0.0062

MetaRNN

Benign

0.12

T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.4

L;.;.

PrimateAI

Benign

0.43

PROVEAN

Benign

-1.4

N;.;.

REVEL

Benign

0.042

Sift

Benign

0.43

T;.;.

Sift4G

Benign

0.43

T;T;T

Polyphen

0.97

D;.;.

Vest4

0.51

MutPred

0.39

Loss of relative solvent accessibility (P = 0.107);.;Loss of relative solvent accessibility (P = 0.107);

MVP

0.16

MPC

0.23

ClinPred

0.25

GERP RS

2.9

Varity_R

0.11

gMVP

0.37

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

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over