rs183372450

Variant names:

• chr6-116628384-C-T
• rs183372450
• NM_001010892.3:c.1662+15C>T

Your query was ambiguous. Multiple possible variants found:

• chr6-116628384-C-T
• chr6-116628384-C-A

Variant summary

Our verdict is Benign. The variant received -9 ACMG points: 0P and 9B. BP4_Strong BP6 BS2

The NM_001010892.3(RSPH4A):​c.1662+15C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00164 in 1,584,112 control chromosomes in the GnomAD database, including 8 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

• Frequency:
  • Genomes: 𝑓 0.0014 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0017 (8 hom.)
• Consequence: RSPH4A NM_001010892.3 intron
• Clinical Significance: Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1 B:2
• Conservation: PhyloP100: -1.98
• Publications: 0 publications found

Genes affected

RSPH4A (HGNC:21558): (radial spoke head component 4A) This gene encodes a protein that appears to be a component the radial spoke head, as determined by homology to similar proteins in the biflagellate alga Chlamydomonas reinhardtii and other ciliates. Radial spokes, which are regularly spaced along cilia, sperm, and flagella axonemes, consist of a thin 'stalk' and a bulbous 'head' that form a signal transduction scaffold between the central pair of microtubules and dynein. Mutations in this gene cause primary ciliary dyskinesia 1, a disease arising from dysmotility of motile cilia and sperm. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Sep 2009]

RSPH4A Gene-Disease associations (from GenCC):

• primary ciliary dyskinesia 11

  Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), PanelApp Australia, Ambry Genetics, ClinGen
• primary ciliary dyskinesia

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

LOC124901386 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -9 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.99).
• BP6: Variant 6-116628384-C-T is Benign according to our data. Variant chr6-116628384-C-T is described in ClinVar as Conflicting_classifications_of_pathogenicity. ClinVar VariationId is 227901.
• BS2: High Homozygotes in GnomAdExome4 at 8 AR,AD gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001010892.3. 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
	RSPH4A	NM_001010892.3	MANE Select	c.1662+15C>T		intron	N/A	NP_001010892.1	Q5TD94-1
	RSPH4A	NM_001161664.2		c.1662+15C>T		intron	N/A	NP_001155136.1	Q5TD94-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RSPH4A	ENST00000229554.10	TSL:1 MANE Select	c.1662+15C>T		intron	N/A	ENSP00000229554.5	Q5TD94-1
	RSPH4A	ENST00000368581.8	TSL:1	c.1662+15C>T		intron	N/A	ENSP00000357570.4	Q5TD94-3
	RSPH4A	ENST00000368580.4	TSL:5	c.922-1183C>T		intron	N/A	ENSP00000357569.4	Q5TD94-2

Frequencies

GnomAD3 genomes AF: 0.00135 AC: 206 AN: 152104 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000507

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000328

Gnomad ASJ AF: 0.00519

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000416

Gnomad FIN AF: 0.00179

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00201

Gnomad OTH AF: 0.00192

GnomAD2 exomes AF: 0.00162 AC: 396 AN: 244194 AF XY: 0.00163

Gnomad AFR exome AF: 0.000316

Gnomad AMR exome AF: 0.000673

Gnomad ASJ exome AF: 0.00336

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00200

Gnomad NFE exome AF: 0.00241

Gnomad OTH exome AF: 0.00201

GnomAD4 exome AF: 0.00167 AC: 2395 AN: 1431890 Hom.: 8 Cov.: 25 AF XY: 0.00172 AC XY: 1226 AN XY: 714268

African (AFR) AF: 0.000274 AC: 9 AN: 32854

American (AMR) AF: 0.000652 AC: 29 AN: 44484

Ashkenazi Jewish (ASJ) AF: 0.00331 AC: 86 AN: 25954

East Asian (EAS) AF: 0.00 AC: 0 AN: 39536

South Asian (SAS) AF: 0.000736 AC: 63 AN: 85640

European-Finnish (FIN) AF: 0.00239 AC: 126 AN: 52808

Middle Eastern (MID) AF: 0.00158 AC: 9 AN: 5700

European-Non Finnish (NFE) AF: 0.00181 AC: 1970 AN: 1085522

Other (OTH) AF: 0.00173 AC: 103 AN: 59392

GnomAD4 genome AF: 0.00135 AC: 206 AN: 152222 Hom.: 0 Cov.: 32 AF XY: 0.00130 AC XY: 97 AN XY: 74422

African (AFR) AF: 0.000506 AC: 21 AN: 41542

American (AMR) AF: 0.000327 AC: 5 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.00519 AC: 18 AN: 3468

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

South Asian (SAS) AF: 0.000416 AC: 2 AN: 4808

European-Finnish (FIN) AF: 0.00179 AC: 19 AN: 10606

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00201 AC: 137 AN: 68022

Other (OTH) AF: 0.00190 AC: 4 AN: 2110

Alfa AF: 0.00203 Hom.: 1

Bravo AF: 0.00124

Asia WGS AF: 0.000866 AC: 3 AN: 3478

ClinVar

ClinVar submissions

Significance: Conflicting classifications of pathogenicity

Revision: criteria provided, conflicting classifications

Pathogenic	VUS	Benign	Condition
-	-	1	not specified (1)
-	-	1	Primary ciliary dyskinesia (1)
-	1	-	Primary ciliary dyskinesia 11 (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	0.013
DANN	Benign	0.18
PhyloP100		-2.0
Mutation Taster		=100/0	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: rs183372450; hg19: chr6-116949547;