5-80320701-A-C

Position:

• chr5-80320701-A-C

Variant summary

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

The NM_032567.4(SPZ1):​c.486A>C​(p.Arg162Ser) 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. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: SPZ1 NM_032567.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.182

Genes affected

SPZ1 (HGNC:30721): (spermatogenic leucine zipper 1) This gene encodes a bHLH-zip transcription factor which functions in the mitogen-activate protein kinase (MAPK) signaling pathway. Because of its role in the upregulation of cell proliferation and tumorigenesis, this gene may serve as a target for Ras-induced tumor treatments. [provided by RefSeq, Oct 2011]

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=0.10017219).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SPZ1	NM_032567.4	c.486A>C	p.Arg162Ser	missense_variant	1/1	ENST00000296739.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SPZ1	ENST00000296739.6	c.486A>C	p.Arg162Ser	missense_variant	1/1		NM_032567.4	P1
SPZ1	ENST00000511881.1	c.486A>C	p.Arg162Ser	missense_variant	2/2	3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 27

GnomAD4 genome Cov.: 32

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 19, 2022

The c.486A>C (p.R162S) alteration is located in exon 1 (coding exon 1) of the SPZ1 gene. This alteration results from a A to C substitution at nucleotide position 486, causing the arginine (R) at amino acid position 162 to be replaced by a serine (S). 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	Uncertain	0.49
BayesDel_addAF	Benign	-0.15	T
BayesDel_noAF	Benign	-0.45
CADD	Benign	14
DANN	Benign	0.88
Eigen	Benign	-0.82
Eigen_PC	Benign	-0.94
FATHMM_MKL	Benign	0.034	N
LIST_S2	Benign	0.42	T;T
M_CAP	Benign	0.0044	T
MetaRNN	Benign	0.10	T;T
MetaSVM	Benign	-1.0	T
MutationTaster	Benign	1.0	N
PrimateAI	Uncertain	0.69	T
PROVEAN	Benign	-0.90	N;N
REVEL	Benign	0.033
Sift	Uncertain	0.0070	D;D
Sift4G	Benign	0.48	T;T
Polyphen		0.83	.;P
Vest4		0.15
MutPred		0.44		Gain of glycosylation at R162 (P = 0.0284);Gain of glycosylation at R162 (P = 0.0284);
MVP		0.23
MPC		0.033
ClinPred		0.14	T
GERP RS		-0.17
Varity_R		0.13
gMVP		0.17

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: chr5-79616520;