7-5928199-G-A

Position:

• chr7-5928199-G-A

Variant summary

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

The NM_173565.5(RSPH10B):​c.2429C>T​(p.Ala810Val) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 34)
  • Exomes 𝑓: 0.000013 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: RSPH10B NM_173565.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.30

Genes affected

RSPH10B (HGNC:27362): (radial spoke head 10 homolog B)

RSPH10B (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RSPH10B	NM_173565.5	c.2429C>T	p.Ala810Val	missense_variant	20/21	ENST00000404406.6	NP_775836.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RSPH10B	ENST00000404406.6	c.2429C>T	p.Ala810Val	missense_variant	20/21	1	NM_173565.5	ENSP00000384097.1

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.0000130 AC: 19 AN: 1460926 Hom.: 0 Cov.: 34 AF XY: 0.0000151 AC XY: 11 AN XY: 726806

Gnomad4 AFR exome AF: 0.000419

Gnomad4 AMR exome AF: 0.0000224

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000116

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.0000497

GnomAD4 genome Cov.: 34

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Aug 02, 2022

The c.2429C>T (p.A810V) alteration is located in exon 20 (coding exon 18) of the RSPH10B gene. This alteration results from a C to T substitution at nucleotide position 2429, causing the alanine (A) at amino acid position 810 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.24
BayesDel_addAF	Benign	-0.074	T
BayesDel_noAF	Benign	-0.34
CADD	Pathogenic	26
DANN	Uncertain	1.0
DEOGEN2	Benign	0.046	T;T;T
Eigen	Uncertain	0.35
Eigen_PC	Uncertain	0.30
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Benign	0.78	T;.;.
M_CAP	Benign	0.051	D
MetaRNN	Benign	0.42	T;T;T
MetaSVM	Benign	-0.72	T
MutationAssessor	Benign	1.9	L;L;L
PrimateAI	Uncertain	0.60	T
PROVEAN	Benign	-1.8	N;N;N
REVEL	Benign	0.14
Sift	Uncertain	0.029	D;D;D
Sift4G	Uncertain	0.0080	D;D;D
Polyphen		0.92	P;P;P
Vest4		0.52
MutPred		0.23		Gain of sheet (P = 0.0477);Gain of sheet (P = 0.0477);Gain of sheet (P = 0.0477);
MVP		0.35
ClinPred		0.89	D
GERP RS		4.8
Varity_R		0.12
gMVP		0.13

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.43		Details are displayed if max score is > 0.2
DS_DG_spliceai		0.43		Position offset: 2

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

Publications

LitVar

Other links and lift over

dbSNP: rs1382909838; hg19: chr7-5967830;