rs753513198

Variant names:

• chr19-45796030-T-A
• rs753513198
• NM_030785.4:c.1993A>T

Your query was ambiguous. Multiple possible variants found:

• chr19-45796030-T-A
• chr19-45796030-T-C
• chr19-45796030-T-G

Variant summary

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

The NM_030785.4(RSPH6A):​c.1993A>T​(p.Ile665Phe) 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. 15/21 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: 31)
• Consequence: RSPH6A NM_030785.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0760

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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.18575507).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RSPH6A	NM_030785.4	c.1993A>T	p.Ile665Phe	missense_variant	Exon 6 of 6	ENST00000221538.8	NP_110412.1
RSPH6A	XM_011527351.3	c.*68A>T		3_prime_UTR_variant	Exon 6 of 6		XP_011525653.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RSPH6A	ENST00000221538.8	c.1993A>T	p.Ile665Phe	missense_variant	Exon 6 of 6	1	NM_030785.4	ENSP00000221538.2
RSPH6A	ENST00000597055.1	c.1989A>T	p.Pro663Pro	synonymous_variant	Exon 6 of 6	1		ENSP00000472630.1
RSPH6A	ENST00000600188.5	c.1201A>T	p.Ile401Phe	missense_variant	Exon 5 of 5	2		ENSP00000471559.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 35

GnomAD4 genome Cov.: 31

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.18
BayesDel_addAF	Benign	-0.24	T
BayesDel_noAF	Benign	-0.59
CADD	Benign	15
DANN	Benign	0.97
DEOGEN2	Benign	0.15	T;.
Eigen	Benign	-0.44
Eigen_PC	Benign	-0.60
FATHMM_MKL	Benign	0.065	N
LIST_S2	Benign	0.67	T;T
M_CAP	Benign	0.0067	T
MetaRNN	Benign	0.19	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.8	L;.
PrimateAI	Benign	0.32	T
PROVEAN	Benign	-2.4	N;.
REVEL	Benign	0.11
Sift	Benign	0.098	T;.
Sift4G	Benign	0.094	T;T
Polyphen		0.83	P;.
Vest4		0.27
MutPred		0.65		Loss of catalytic residue at I665 (P = 0.0367);.;
MVP		0.055
MPC		0.24
ClinPred		0.49	T
GERP RS		-4.2
Varity_R		0.20
gMVP		0.52

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: rs753513198; hg19: chr19-46299288;