7-5926424-C-T

Position:

• chr7-5926424-C-T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_173565.5(RSPH10B):​c.2557G>A​(p.Asp853Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 20)
  • Exomes 𝑓: 7.0e-7 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: RSPH10B NM_173565.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.52

Genes affected

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

CCZ1 (HGNC:21691): (CCZ1 homolog, vacuolar protein trafficking and biogenesis associated) Enables guanyl-nucleotide exchange factor activity. Predicted to be involved in vesicle-mediated transport. Located in intracellular membrane-bounded organelle. Part of Mon1-Ccz1 complex. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.1788136).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RSPH10B	NM_173565.5	c.2557G>A	p.Asp853Asn	missense_variant	21/21	ENST00000404406.6	NP_775836.4
CCZ1	NM_015622.6	c.*737C>T		3_prime_UTR_variant	15/15	ENST00000325974.9	NP_056437.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RSPH10B	ENST00000404406.6	c.2557G>A	p.Asp853Asn	missense_variant	21/21	1	NM_173565.5	ENSP00000384097.1
CCZ1	ENST00000325974.9	c.*737C>T		3_prime_UTR_variant	15/15	1	NM_015622.6	ENSP00000325681.6

Frequencies

GnomAD3 genomes Cov.: 20

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 7.03e-7 AC: 1 AN: 1422444 Hom.: 0 Cov.: 29 AF XY: 0.00 AC XY: 0 AN XY: 708556

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

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: 9.28e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 20

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

Apr 24, 2024

The c.2557G>A (p.D853N) alteration is located in exon 21 (coding exon 19) of the RSPH10B gene. This alteration results from a G to A substitution at nucleotide position 2557, causing the aspartic acid (D) at amino acid position 853 to be replaced by an asparagine (N). 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	0.081
BayesDel_addAF	Benign	-0.22	T
BayesDel_noAF	Benign	-0.55
CADD	Benign	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.022	T;T;T
Eigen	Uncertain	0.34
Eigen_PC	Uncertain	0.28
FATHMM_MKL	Uncertain	0.91	D
LIST_S2	Benign	0.62	T;.;.
M_CAP	Benign	0.029	D
MetaRNN	Benign	0.18	T;T;T
MetaSVM	Benign	-0.76	T
MutationAssessor	Benign	1.8	L;L;L
PrimateAI	Benign	0.47	T
PROVEAN	Benign	-1.8	N;N;N
REVEL	Benign	0.18
Sift	Uncertain	0.0070	D;D;D
Sift4G	Uncertain	0.048	D;D;D
Polyphen		0.98	D;D;D
Vest4		0.21
MutPred		0.20		Gain of MoRF binding (P = 0.0812);Gain of MoRF binding (P = 0.0812);Gain of MoRF binding (P = 0.0812);
MVP		0.42
ClinPred		0.92	D
GERP RS		4.4
Varity_R		0.14
gMVP		0.077

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: rs1219564359; hg19: chr7-5966055;