NM_031924.8:c.10_12delGCGinsACC

Variant names:

• chr6-158999539-CGC-GGT
• NM_031924.8:c.10_12delGCGinsACC
• RSPH3 p.Ala4Thr

Variant summary

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

The NM_031924.8(RSPH3):​c.10_12delGCGinsACC​(p.Ala4Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. It is difficult to determine the true allele frequency of this variant because it is of type MNV, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar. Synonymous variant affecting the same amino acid position (i.e. A4A) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: RSPH3 NM_031924.8 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.22
• Publications: 0 publications found

Genes affected

RSPH3 (HGNC:21054): (radial spoke head 3) The protein encoded by this gene acts as a protein kinase A anchoring protein. Mutations in this gene cause primary ciliary dyskinesia; a disorder characterized by defects of the axoneme in motile cilia and sperm flagella. The homolog of this gene was first identified in the blue-green algae Chlamydomonas as encoding a radial spoke protein that formed a structural component of motile cilia and flagella. Alternate splicing results in multiple transcript variants encoding distinct isoforms. [provided by RefSeq, Dec 2016]

TAGAP-AS1 (HGNC:55239): (TAGAP antisense RNA 1)

ACMG classification

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_031924.8. 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
	RSPH3	NM_031924.8	MANE Select	c.10_12delGCGinsACC	p.Ala4Thr	missense	N/A	NP_114130.4
	RSPH3	NM_001346418.1		c.436_438delGCGinsACC	p.Ala146Thr	missense	N/A	NP_001333347.1	Q86UC2-2
	RSPH3	NR_144434.1		n.647_649delGCGinsACC		non_coding_transcript_exon	Exon 1 of 9

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RSPH3	ENST00000367069.7	TSL:1 MANE Select	c.10_12delGCGinsACC	p.Ala4Thr	missense	N/A	ENSP00000356036.1	A0A0C4DFU3
	RSPH3	ENST00000884885.1		c.10_12delGCGinsACC	p.Ala4Thr	missense	N/A	ENSP00000554944.1
	RSPH3	ENST00000449822.6	TSL:2	c.10_12delGCGinsACC	p.Ala4Thr	missense	N/A	ENSP00000393195.1	A0A0C4DG29

Frequencies

GnomAD3 genomes Cov.: 32

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		1.2

Splicing

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr6-159420571;