chr19-45800468-C-T

Variant names:

• chr19-45800468-C-T
• rs200210042
• NM_030785.4:c.1894G>A

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_030785.4(RSPH6A):​c.1894G>A​(p.Ala632Thr) variant causes a missense change. The variant allele was found at a frequency of 0.00000616 in 1,460,588 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000062 (0 hom.)
• Consequence: RSPH6A NM_030785.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.20

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.853

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RSPH6A	NM_030785.4	c.1894G>A	p.Ala632Thr	missense_variant	Exon 5 of 6	ENST00000221538.8	NP_110412.1
RSPH6A	XM_011527351.3	c.1894G>A	p.Ala632Thr	missense_variant	Exon 5 of 6		XP_011525653.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RSPH6A	ENST00000221538.8	c.1894G>A	p.Ala632Thr	missense_variant	Exon 5 of 6	1	NM_030785.4	ENSP00000221538.2
RSPH6A	ENST00000597055.1	c.1894G>A	p.Ala632Thr	missense_variant	Exon 5 of 6	1		ENSP00000472630.1
RSPH6A	ENST00000600188.5	c.1102G>A	p.Ala368Thr	missense_variant	Exon 4 of 5	2		ENSP00000471559.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.0000120 AC: 3 AN: 249618 Hom.: 0 AF XY: 0.00000741 AC XY: 1 AN XY: 135032

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: 0.0000327

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000177

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000616 AC: 9 AN: 1460588 Hom.: 0 Cov.: 31 AF XY: 0.00000551 AC XY: 4 AN XY: 726576

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: 0.0000348

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000540

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

Alfa AF: 0.0000326 Hom.: 0

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000116 AC: 1

ExAC AF: 0.0000165 AC: 2

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.73
BayesDel_addAF	Benign	-0.064	T
BayesDel_noAF	Benign	-0.23
CADD	Pathogenic	27
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.30	T;.;T
Eigen	Pathogenic	0.68
Eigen_PC	Uncertain	0.59
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Pathogenic	0.98	D;D;D
M_CAP	Benign	0.082	D
MetaRNN	Pathogenic	0.85	D;D;D
MetaSVM	Benign	-0.56	T
MutationAssessor	Pathogenic	3.4	M;.;.
PrimateAI	Uncertain	0.62	T
PROVEAN	Uncertain	-3.5	D;.;.
REVEL	Uncertain	0.29
Sift	Uncertain	0.0020	D;.;.
Sift4G	Uncertain	0.0030	D;D;D
Polyphen		0.99	D;.;.
Vest4		0.77
MVP		0.33
MPC		0.48
ClinPred		0.95	D
GERP RS		4.0
Varity_R		0.52
gMVP		0.79

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

Other links and lift over

dbSNP: rs200210042; hg19: chr19-46303726;