7-5928308-A-C

Position:

• chr7-5928308-A-C

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 1P and 0B. PP3

The NM_173565.5(RSPH10B):​c.2320T>G​(p.Phe774Val) variant causes a missense change. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.0 (0 hom., cov: 34)
  • Exomes 𝑓: 0.0000021 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: RSPH10B NM_173565.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.83

Genes affected

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

RSPH10B (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PP3: MetaRNN computational evidence supports a deleterious effect, 0.777

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RSPH10B	NM_173565.5	c.2320T>G	p.Phe774Val	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.2320T>G	p.Phe774Val	missense_variant	20/21	1	NM_173565.5	ENSP00000384097.1

Frequencies

GnomAD3 genomes AF: 0.00 AC: 0 AN: 151748 Hom.: 0 Cov.: 34 FAILED QC

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

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

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00000205 AC: 3 AN: 1461450 Hom.: 0 Cov.: 34 AF XY: 0.00000275 AC XY: 2 AN XY: 727024

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.0000672

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 151748 Hom.: 0 Cov.: 34 AF XY: 0.00 AC XY: 0 AN XY: 74130

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00

Gnomad4 OTH AF: 0.00

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

Dec 06, 2021

The c.2320T>G (p.F774V) alteration is located in exon 20 (coding exon 18) of the RSPH10B gene. This alteration results from a T to G substitution at nucleotide position 2320, causing the phenylalanine (F) at amino acid position 774 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	Pathogenic	0.60
BayesDel_addAF	Pathogenic	0.18	D
BayesDel_noAF	Uncertain	0.020
CADD	Benign	23
DANN	Uncertain	0.99
DEOGEN2	Benign	0.17	T;T;T
Eigen	Uncertain	0.43
Eigen_PC	Uncertain	0.30
FATHMM_MKL	Uncertain	0.90	D
LIST_S2	Benign	0.72	T;.;.
M_CAP	Uncertain	0.24	D
MetaRNN	Pathogenic	0.78	D;D;D
MetaSVM	Uncertain	-0.078	T
MutationAssessor	Benign	1.9	L;L;L
PrimateAI	Uncertain	0.75	T
PROVEAN	Uncertain	-4.0	D;D;D
REVEL	Uncertain	0.50
Sift	Pathogenic	0.0	D;D;D
Sift4G	Pathogenic	0.0	D;D;D
Polyphen		1.0	D;D;D
Vest4		0.80
MutPred		0.45		Gain of MoRF binding (P = 0.0853);Gain of MoRF binding (P = 0.0853);Gain of MoRF binding (P = 0.0853);
MVP		0.55
ClinPred		0.98	D
GERP RS		4.9
Varity_R		0.45
gMVP		0.37

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

Publications

LitVar

Other links and lift over

dbSNP: rs1285659038; hg19: chr7-5967939;