rs1554249521

Variant names:

• chr6-116629594-C-A
• NM_001010892.3:c.1690C>A

Your query was ambiguous. Multiple possible variants found:

• chr6-116629594-C-A
• chr6-116629594-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001010892.3(RSPH4A):​c.1690C>A​(p.Gln564Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000685 in 1,459,988 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 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: RSPH4A NM_001010892.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.85

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]

LOC124901386 (HGNC:):

ACMG classification

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=0.15292904).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RSPH4A	NM_001010892.3	c.1690C>A	p.Gln564Lys	missense_variant	Exon 4 of 6	ENST00000229554.10	NP_001010892.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RSPH4A	ENST00000229554.10	c.1690C>A	p.Gln564Lys	missense_variant	Exon 4 of 6	1	NM_001010892.3	ENSP00000229554.5
RSPH4A	ENST00000368581.8	c.1663-841C>A		intron_variant	Intron 3 of 4	1		ENSP00000357570.4
RSPH4A	ENST00000368580.4	c.949C>A	p.Gln317Lys	missense_variant	Exon 3 of 5	5		ENSP00000357569.4

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.85e-7 AC: 1 AN: 1459988 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 726428

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: 0.0000116

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.082
BayesDel_addAF	Benign	-0.27	T
BayesDel_noAF	Benign	-0.63
CADD	Benign	18
DANN	Benign	0.94
DEOGEN2	Benign	0.0019	T;.
Eigen	Benign	-0.34
Eigen_PC	Benign	-0.21
FATHMM_MKL	Uncertain	0.78	D
LIST_S2	Benign	0.72	T;T
M_CAP	Benign	0.0080	T
MetaRNN	Benign	0.15	T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.2	L;.
PrimateAI	Uncertain	0.50	T
PROVEAN	Uncertain	-2.6	D;D
REVEL	Benign	0.088
Sift	Benign	0.46	T;T
Sift4G	Benign	0.26	T;T
Polyphen		0.078	B;.
Vest4		0.26
MutPred		0.52		Gain of methylation at Q564 (P = 0.0051);.;
MVP		0.18
MPC		0.51
ClinPred		0.64	D
GERP RS		5.2
Varity_R		0.36
gMVP		0.27

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr6-116950757; COSMIC: COSV57634450;