17-45255704-C-A

Position:

• chr17-45255704-C-A

Variant summary

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

The NM_152343.3(SPATA32):​c.478G>T​(p.Ala160Ser) 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. 15/21 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: SPATA32 NM_152343.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.522

Genes affected

SPATA32 (HGNC:26349): (spermatogenesis associated 32) Predicted to enable actin binding activity. Predicted to be involved in spermatogenesis. Predicted to be active in perinuclear region of cytoplasm. [provided by Alliance of Genome Resources, Apr 2022]

MAP3K14-AS1 (HGNC:):

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=0.13020828).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SPATA32	NM_152343.3	c.478G>T	p.Ala160Ser	missense_variant	4/5	ENST00000331780.5	NP_689556.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SPATA32	ENST00000331780.5	c.478G>T	p.Ala160Ser	missense_variant	4/5	1	NM_152343.3	ENSP00000331532.4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

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

Nov 13, 2023

The c.478G>T (p.A160S) alteration is located in exon 4 (coding exon 4) of the SPATA32 gene. This alteration results from a G to T substitution at nucleotide position 478, causing the alanine (A) at amino acid position 160 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	Benign	0.17
BayesDel_addAF	Benign	-0.14	T
BayesDel_noAF	Benign	-0.44
CADD	Benign	21
DANN	Uncertain	0.99
DEOGEN2	Benign	0.022	T
Eigen	Benign	-0.15
Eigen_PC	Benign	-0.097
FATHMM_MKL	Benign	0.69	D
LIST_S2	Benign	0.45	T
M_CAP	Benign	0.0071	T
MetaRNN	Benign	0.13	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.3	L
PrimateAI	Benign	0.28	T
PROVEAN	Benign	-0.57	N
REVEL	Benign	0.059
Sift	Benign	0.52	T
Sift4G	Benign	0.45	T
Polyphen		0.87	P
Vest4		0.15
MutPred		0.37		Loss of helix (P = 0.0072);
MVP		0.26
MPC		0.67
ClinPred		0.90	D
GERP RS		2.0
Varity_R		0.057
gMVP		0.098

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: chr17-43333071;