NM_001010892.3:c.2101G>C

Variant names:

Variant summary

Our verdict is Benign. The variant received -9 ACMG points: 0P and 9B. BP4_StrongBP6BS2

The NM_001010892.3(RSPH4A):c.2101G>C(p.Glu701Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000249 in 1,613,992 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

Frequency

Genomes: 𝑓 0.0014 ( 2 hom., cov: 32)

Exomes 𝑓: 0.00013 ( 0 hom. )

Consequence

RSPH4A
NM_001010892.3 missense

Scores

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:3B:3

Conservation

PhyloP100: 2.77

Publications

1 publications found

Variant links:

Genes affected

RSPH4A (HGNC:21558): (radial spoke head component 4A) This gene encodes a protein that appears to be a component the radial spoke head, as determined by homology to similar proteins in the biflagellate alga Chlamydomonas reinhardtii and other ciliates. Radial spokes, which are regularly spaced along cilia, sperm, and flagella axonemes, consist of a thin 'stalk' and a bulbous 'head' that form a signal transduction scaffold between the central pair of microtubules and dynein. Mutations in this gene cause primary ciliary dyskinesia 1, a disease arising from dysmotility of motile cilia and sperm. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Sep 2009]

RSPH4A Gene-Disease associations (from GenCC):

primary ciliary dyskinesia 11
Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), PanelApp Australia, Ambry Genetics, ClinGen
primary ciliary dyskinesia
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

RSPH4A links:

LOC124901386 (HGNC:):

LOC124901386 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -9 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0046696067).

BP6

Variant 6-116632391-G-C is Benign according to our data. Variant chr6-116632391-G-C is described in ClinVar as Conflicting_classifications_of_pathogenicity. ClinVar VariationId is 355125.

BS2

High Homozygotes in GnomAd4 at 2 AR,AD gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001010892.3. 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
	RSPH4A	NM_001010892.3	MANE Select	c.2101G>C	p.Glu701Gln	missense	Exon 6 of 6	NP_001010892.1	Q5TD94-1
	RSPH4A	NM_001161664.2		c.*162G>C		3_prime_UTR	Exon 5 of 5	NP_001155136.1	Q5TD94-3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
RSPH4A	ENST00000229554.10	TSL:1 MANE Select	c.2101G>C	p.Glu701Gln	missense	Exon 6 of 6	ENSP00000229554.5	Q5TD94-1
RSPH4A	ENST00000368581.8	TSL:1	c.*162G>C		3_prime_UTR	Exon 5 of 5	ENSP00000357570.4	Q5TD94-3
RSPH4A	ENST00000368580.4	TSL:5	c.1360G>C	p.Glu454Gln	missense	Exon 5 of 5	ENSP00000357569.4	Q5TD94-2

Frequencies

GnomAD3 genomes

AF:

0.00143

AC:

218

AN:

152150

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00507

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000393

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:

0.0000147

Gnomad OTH

AF:

0.000478

GnomAD2 exomes

AF:

0.000406

AC:

102

AN:

251138

AF XY:

0.000258

show subpopulations

Gnomad AFR exome

AF:

0.00511

Gnomad AMR exome

AF:

0.000464

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000176

Gnomad OTH exome

AF:

0.000163

GnomAD4 exome

AF:

0.000126

AC:

184

AN:

1461724

Hom.:

Cov.:

AF XY:

0.0000853

AC XY:

AN XY:

727162

show subpopulations

African (AFR)

AF:

0.00418

AC:

140

AN:

33478

American (AMR)

AF:

0.000515

AC:

AN:

44700

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26132

East Asian (EAS)

AF:

0.00

AC:

AN:

39688

South Asian (SAS)

AF:

0.00

AC:

AN:

86230

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53410

Middle Eastern (MID)

AF:

0.000173

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.00000270

AC:

AN:

1111930

Other (OTH)

AF:

0.000282

AC:

AN:

60388

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.477

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00143

AC:

218

AN:

152268

Hom.:

Cov.:

AF XY:

0.00160

AC XY:

119

AN XY:

74464

show subpopulations

African (AFR)

AF:

0.00505

AC:

210

AN:

41554

American (AMR)

AF:

0.000393

AC:

AN:

15282

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5184

South Asian (SAS)

AF:

0.00

AC:

AN:

4826

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10612

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0000147

AC:

AN:

68020

Other (OTH)

AF:

0.000473

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.495

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0000788

Hom.:

Bravo

AF:

0.00168

ESP6500AA

AF:

0.00613

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.000478

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3478

ClinVar

ClinVar submissions

Significance:Conflicting classifications of pathogenicity

Revision:criteria provided, conflicting classifications

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

Primary ciliary dyskinesia (2)

Primary ciliary dyskinesia 11 (1)

RSPH4A-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.13

BayesDel_addAF

Benign

-0.55

BayesDel_noAF

Benign

-0.56

CADD

Benign

(source)

DANN

Benign

0.91

DEOGEN2

Benign

0.12

Eigen

Benign

-0.56

Eigen_PC

Benign

-0.53

FATHMM_MKL

Uncertain

0.93

LIST_S2

Benign

0.41

M_CAP

Benign

0.0088

MetaRNN

Benign

0.0047

MetaSVM

Benign

-1.1

MutationAssessor

Uncertain

2.4

PhyloP100

2.8

PrimateAI

Benign

0.29

PROVEAN

Uncertain

-2.4

REVEL

Benign

0.17

Sift

Benign

0.53

Sift4G

Uncertain

0.033

Polyphen

0.030

Vest4

0.069

MVP

0.53

MPC

0.14

ClinPred

0.029

GERP RS

0.11

Varity_R

0.13

gMVP

0.48

Mutation Taster

=93/7

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over