7-5928385-T-C

Position:

• chr7-5928385-T-C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The ENST00000404406.6(RSPH10B):​c.2243A>G​(p.Glu748Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 35)
  • Exomes 𝑓: 0.0000021 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: RSPH10B ENST00000404406.6 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.33

Genes affected

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

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.16067147).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RSPH10B	NM_173565.5	c.2243A>G	p.Glu748Gly	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.2243A>G	p.Glu748Gly	missense_variant	20/21	1	NM_173565.5	ENSP00000384097	P1

Frequencies

GnomAD3 genomes Cov.: 35

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00000205 AC: 3 AN: 1461146 Hom.: 0 Cov.: 34 AF XY: 0.00 AC XY: 0 AN XY: 726882

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.0000448

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: 0.0000166

GnomAD4 genome Cov.: 35

Bravo AF: 0.00000378

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

Jan 08, 2024

The c.2243A>G (p.E748G) alteration is located in exon 20 (coding exon 18) of the RSPH10B gene. This alteration results from a A to G substitution at nucleotide position 2243, causing the glutamic acid (E) at amino acid position 748 to be replaced by a glycine (G). 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	0.089
BayesDel_addAF	Benign	-0.083	T
BayesDel_noAF	Benign	-0.36
CADD	Benign	19
DANN	Uncertain	1.0
DEOGEN2	Benign	0.065	T;T;T
Eigen	Benign	0.0070
Eigen_PC	Benign	-0.045
FATHMM_MKL	Benign	0.51	D
LIST_S2	Benign	0.41	T;.;.
M_CAP	Uncertain	0.13	D
MetaRNN	Benign	0.16	T;T;T
MetaSVM	Benign	-0.74	T
MutationAssessor	Benign	1.8	L;L;L
MutationTaster	Benign	1.0	D;N;N;N;N
PrimateAI	Uncertain	0.69	T
PROVEAN	Uncertain	-3.3	D;D;D
REVEL	Benign	0.18
Sift	Uncertain	0.0050	D;D;D
Sift4G	Uncertain	0.0030	D;D;D
Polyphen		0.036	B;B;B
Vest4		0.36
MutPred		0.14		Loss of ubiquitination at K745 (P = 0.0368);Loss of ubiquitination at K745 (P = 0.0368);Loss of ubiquitination at K745 (P = 0.0368);
MVP		0.37
ClinPred		0.95	D
GERP RS		5.0
Varity_R		0.26
gMVP		0.14

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: rs1779631000; hg19: chr7-5968016;