7-5926486-G-A

Position:

• chr7-5926486-G-A

Variant summary

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

The ENST00000404406.6(RSPH10B):​c.2495C>T​(p.Thr832Ile) 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. 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)
• Consequence: RSPH10B ENST00000404406.6 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.427

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 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=0.17181733).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RSPH10B	NM_173565.5	c.2495C>T	p.Thr832Ile	missense_variant	21/21	ENST00000404406.6	NP_775836.4
CCZ1	NM_015622.6	c.*799G>A		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.2495C>T	p.Thr832Ile	missense_variant	21/21	1	NM_173565.5	ENSP00000384097	P1
CCZ1	ENST00000325974.9	c.*799G>A		3_prime_UTR_variant	15/15	1	NM_015622.6	ENSP00000325681	P1

Frequencies

GnomAD3 genomes Cov.: 20

GnomAD4 exome Cov.: 31

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

Aug 09, 2021

The c.2495C>T (p.T832I) alteration is located in exon 21 (coding exon 19) of the RSPH10B gene. This alteration results from a C to T substitution at nucleotide position 2495, causing the threonine (T) at amino acid position 832 to be replaced by an isoleucine (I). 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	0.21
BayesDel_addAF	Benign	-0.17	T
BayesDel_noAF	Benign	-0.49
CADD	Benign	12
DANN	Uncertain	0.99
DEOGEN2	Benign	0.028	T;T;T
Eigen	Benign	-0.56
Eigen_PC	Benign	-0.71
FATHMM_MKL	Benign	0.037	N
LIST_S2	Benign	0.66	T;.;.
M_CAP	Benign	0.018	T
MetaRNN	Benign	0.17	T;T;T
MetaSVM	Benign	-0.94	T
MutationAssessor	Benign	1.6	L;L;L
MutationTaster	Benign	1.0	N;N;N;N;N
PrimateAI	Uncertain	0.57	T
PROVEAN	Benign	-1.8	N;N;N
REVEL	Benign	0.11
Sift	Uncertain	0.0060	D;D;D
Sift4G	Uncertain	0.010	D;D;D
Polyphen		0.80	P;P;P
Vest4		0.36
MutPred		0.37		Loss of disorder (P = 0.0769);Loss of disorder (P = 0.0769);Loss of disorder (P = 0.0769);
MVP		0.17
ClinPred		0.16	T
GERP RS		2.5
Varity_R		0.055
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

No publications associated with this variant yet.

Other links and lift over

hg19: chr7-5966117;