5-139402682-C-G

Position:

• chr5-139402682-C-G

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_194296.2(SPATA24):​c.129G>C​(p.Gln43His) 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. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: SPATA24 NM_194296.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.52

Genes affected

SPATA24 (HGNC:27322): (spermatogenesis associated 24) Predicted to enable DNA binding activity and identical protein binding activity. Predicted to be involved in cell differentiation and spermatogenesis. Located in cytosol and nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.38842618).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SPATA24	NM_194296.2	c.129G>C	p.Gln43His	missense_variant	2/6	ENST00000450845.7	NP_919272.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SPATA24	ENST00000450845.7	c.129G>C	p.Gln43His	missense_variant	2/6	1	NM_194296.2	ENSP00000414920.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

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

Aug 09, 2021

The c.129G>C (p.Q43H) alteration is located in exon 2 (coding exon 2) of the SPATA24 gene. This alteration results from a G to C substitution at nucleotide position 129, causing the glutamine (Q) at amino acid position 43 to be replaced by a histidine (H). 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	Pathogenic	0.62
BayesDel_addAF	Uncertain	0.062	T
BayesDel_noAF	Benign	-0.15
CADD	Benign	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.032	T;T;.;T
Eigen	Benign	-0.27
Eigen_PC	Benign	-0.20
FATHMM_MKL	Uncertain	0.85	D
LIST_S2	Benign	0.77	T;T;T;T
M_CAP	Benign	0.0064	T
MetaRNN	Benign	0.39	T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.69	.;N;N;.
PrimateAI	Uncertain	0.67	T
PROVEAN	Benign	-2.1	N;D;D;D
REVEL	Uncertain	0.48
Sift	Uncertain	0.0070	D;D;D;D
Sift4G	Benign	0.12	.;T;T;T
Polyphen		1.0	D;D;D;.
Vest4		0.41, 0.56, 0.54
MutPred		0.50		Gain of catalytic residue at D44 (P = 0.0792);Gain of catalytic residue at D44 (P = 0.0792);Gain of catalytic residue at D44 (P = 0.0792);Gain of catalytic residue at D44 (P = 0.0792);
MVP		0.014
ClinPred		0.79	D
GERP RS		2.1
Varity_R		0.12

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs1758851964; hg19: chr5-138738371;