chr19-45795920-C-T

Variant names:

• chr19-45795920-C-T
• rs61730714
• NM_030785.4:c.2103G>A

Variant summary

Our verdict is Benign. The variant received -19 ACMG points: 0P and 19B. BP4_Moderate BP6_Very_Strong BP7 BA1

The NM_030785.4(RSPH6A):​c.2103G>A​(p.Glu701Glu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00584 in 1,613,748 control chromosomes in the GnomAD database, including 444 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.030 (220 hom., cov: 31)
  • Exomes 𝑓: 0.0033 (224 hom.)
• Consequence: RSPH6A NM_030785.4 synonymous
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 1.88
• Publications: 1 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: Benign. The variant received -19 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.41).
• BP6: Variant 19-45795920-C-T is Benign according to our data. Variant chr19-45795920-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 780576.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=1.88 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.102 is higher than 0.05.

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.2103G>A	p.Glu701Glu	synonymous	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.2103G>A	p.Glu701Glu	synonymous	Exon 6 of 6	ENSP00000221538.2	Q9H0K4
	RSPH6A	ENST00000597055.1	TSL:1	c.*68G>A		3_prime_UTR	Exon 6 of 6	ENSP00000472630.1	M0R2K1
	RSPH6A	ENST00000600188.5	TSL:2	c.1311G>A	p.Glu437Glu	synonymous	Exon 5 of 5	ENSP00000471559.1	M0R103

Frequencies

GnomAD3 genomes AF: 0.0303 AC: 4600 AN: 152024 Hom.: 221 Cov.: 31

Gnomad AFR AF: 0.105

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0111

Gnomad ASJ AF: 0.000866

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.000559

Gnomad OTH AF: 0.0220

GnomAD2 exomes AF: 0.00789 AC: 1978 AN: 250680 AF XY: 0.00578

Gnomad AFR exome AF: 0.107

Gnomad AMR exome AF: 0.00524

Gnomad ASJ exome AF: 0.000794

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000362

Gnomad OTH exome AF: 0.00294

GnomAD4 exome AF: 0.00330 AC: 4826 AN: 1461608 Hom.: 224 Cov.: 35 AF XY: 0.00281 AC XY: 2044 AN XY: 727116

African (AFR) AF: 0.110 AC: 3694 AN: 33478

American (AMR) AF: 0.00599 AC: 268 AN: 44716

Ashkenazi Jewish (ASJ) AF: 0.000957 AC: 25 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39698

South Asian (SAS) AF: 0.000174 AC: 15 AN: 86228

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53238

Middle Eastern (MID) AF: 0.00191 AC: 11 AN: 5746

European-Non Finnish (NFE) AF: 0.000313 AC: 348 AN: 1111978

Other (OTH) AF: 0.00770 AC: 465 AN: 60390

GnomAD4 genome AF: 0.0303 AC: 4603 AN: 152140 Hom.: 220 Cov.: 31 AF XY: 0.0298 AC XY: 2216 AN XY: 74390

African (AFR) AF: 0.105 AC: 4344 AN: 41494

American (AMR) AF: 0.0111 AC: 169 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.000866 AC: 3 AN: 3464

East Asian (EAS) AF: 0.00 AC: 0 AN: 5174

South Asian (SAS) AF: 0.000208 AC: 1 AN: 4818

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10608

Middle Eastern (MID) AF: 0.00680 AC: 2 AN: 294

European-Non Finnish (NFE) AF: 0.000559 AC: 38 AN: 67986

Other (OTH) AF: 0.0218 AC: 46 AN: 2114

Alfa AF: 0.0170 Hom.: 63

Bravo AF: 0.0347

Asia WGS AF: 0.00520 AC: 18 AN: 3478

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.41
CADD	Benign	3.3
DANN	Benign	0.58
PhyloP100		1.9
Mutation Taster		=100/0	polymorphism (auto)

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: rs61730714; hg19: chr19-46299178;