19-45795879-G-T

Variant names:

• chr19-45795879-G-T
• rs776710136
• NM_030785.4:c.2144C>A

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_030785.4(RSPH6A):​c.2144C>A​(p.Thr715Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000141 in 1,272,658 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.0000080 (0 hom., cov: 30)
  • Exomes 𝑓: 0.000015 (0 hom.)
• Consequence: RSPH6A NM_030785.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -1.38
• 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: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.018526226).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_030785.4. 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.2144C>A	p.Thr715Lys	missense	Exon 6 of 6	NP_110412.1	Q9H0K4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RSPH6A	ENST00000221538.8	TSL:1 MANE Select	c.2144C>A	p.Thr715Lys	missense	Exon 6 of 6	ENSP00000221538.2	Q9H0K4
	RSPH6A	ENST00000597055.1	TSL:1	c.*109C>A		3_prime_UTR	Exon 6 of 6	ENSP00000472630.1	M0R2K1
	RSPH6A	ENST00000600188.5	TSL:2	c.1352C>A	p.Thr451Lys	missense	Exon 5 of 5	ENSP00000471559.1	M0R103

Frequencies

GnomAD3 genomes AF: 0.00000797 AC: 1 AN: 125532 Hom.: 0 Cov.: 30

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000830

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: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000833 AC: 16 AN: 192064 AF XY: 0.0000673

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000679

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000148 AC: 17 AN: 1147126 Hom.: 0 Cov.: 30 AF XY: 0.0000123 AC XY: 7 AN XY: 570550

African (AFR) AF: 0.00 AC: 0 AN: 24854

American (AMR) AF: 0.000535 AC: 17 AN: 31784

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 22892

East Asian (EAS) AF: 0.00 AC: 0 AN: 16182

South Asian (SAS) AF: 0.00 AC: 0 AN: 61292

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 42840

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4358

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 896342

Other (OTH) AF: 0.00 AC: 0 AN: 46582

GnomAD4 genome AF: 0.00000797 AC: 1 AN: 125532 Hom.: 0 Cov.: 30 AF XY: 0.0000164 AC XY: 1 AN XY: 60920

African (AFR) AF: 0.00 AC: 0 AN: 33418

American (AMR) AF: 0.0000830 AC: 1 AN: 12048

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3118

East Asian (EAS) AF: 0.00 AC: 0 AN: 2630

South Asian (SAS) AF: 0.00 AC: 0 AN: 3720

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 8988

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 264

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 58838

Other (OTH) AF: 0.00 AC: 0 AN: 1700

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000756

ExAC AF: 0.0000412 AC: 5

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.30	T
BayesDel_noAF	Benign	-0.67
CADD	Benign	0.42
DANN	Benign	0.75
DEOGEN2	Benign	0.0099	T
Eigen	Benign	-1.3
Eigen_PC	Benign	-1.4
FATHMM_MKL	Benign	0.015	N
LIST_S2	Benign	0.41	T
M_CAP	Benign	0.012	T
MetaRNN	Benign	0.019	T
MetaSVM	Benign	-0.97	T
MutationAssessor	Benign	0.69	N
PhyloP100		-1.4
PrimateAI	Benign	0.30	T
PROVEAN	Benign	-0.49	N
REVEL	Benign	0.058
Sift	Pathogenic	0.0	D
Sift4G	Benign	0.20	T
Polyphen		0.017	B
Vest4		0.18
MutPred		0.19		Loss of phosphorylation at T715 (P = 0.0013)
MVP		0.014
MPC		0.24
ClinPred		0.12	T
GERP RS		-3.6
Varity_R		0.19
gMVP		0.12
Mutation Taster		=96/4	polymorphism

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

Other links and lift over

dbSNP: rs776710136; hg19: chr19-46299137;