19-45796070-C-T

Variant names:

• chr19-45796070-C-T
• rs1307712660
• ENST00000597055.1:c.1949G>A

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The ENST00000597055.1(RSPH6A):​c.1949G>A​(p.Ser650Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 10/13 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. S650T) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 31)
• Consequence: RSPH6A ENST00000597055.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.01
• Publications: 0 publications found

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

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.12958819).

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000597055.1. 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
	RSPH6A	NM_030785.4	MANE Select	c.1953G>A	p.Lys651Lys	synonymous	Exon 6 of 6	NP_110412.1	Q9H0K4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RSPH6A	ENST00000597055.1	TSL:1	c.1949G>A	p.Ser650Asn	missense	Exon 6 of 6	ENSP00000472630.1	M0R2K1
	RSPH6A	ENST00000221538.8	TSL:1 MANE Select	c.1953G>A	p.Lys651Lys	synonymous	Exon 6 of 6	ENSP00000221538.2	Q9H0K4
	RSPH6A	ENST00000600188.5	TSL:2	c.1161G>A	p.Lys387Lys	synonymous	Exon 5 of 5	ENSP00000471559.1	M0R103

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 34

GnomAD4 genome Cov.: 31

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.12	T
BayesDel_noAF	Benign	-0.40
CADD	Benign	7.8
DANN	Benign	0.81
DEOGEN2	Benign	0.0034	T
FATHMM_MKL	Benign	0.62	D
LIST_S2	Benign	0.22	T
M_CAP	Benign	0.0024	T
MetaRNN	Benign	0.13	T
PhyloP100		2.0
Sift4G	Benign	0.21	T
Vest4		0.26
MVP		0.47
GERP RS		3.2
Mutation Taster		=77/23	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs1307712660; hg19: chr19-46299328;