1-16399419-A-G

Position:

• chr1-16399419-A-G

Variant summary

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

The NM_198546.1(SPATA21):​c.1277T>C​(p.Leu426Pro) 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. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: SPATA21 NM_198546.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.61

Genes affected

SPATA21 (HGNC:28026): (spermatogenesis associated 21) Predicted to enable calcium ion binding activity. [provided by Alliance of Genome Resources, Apr 2022]

SPATA21 (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=0.13653925).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SPATA21	NM_198546.1	c.1277T>C	p.Leu426Pro	missense_variant	12/13	ENST00000335496.5	NP_940948.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SPATA21	ENST00000335496.5	c.1277T>C	p.Leu426Pro	missense_variant	12/13	1	NM_198546.1	ENSP00000335612.1
SPATA21	ENST00000540400.1	c.1208T>C	p.Leu403Pro	missense_variant	10/11	1		ENSP00000440046.1
SPATA21	ENST00000491418.5	c.401T>C	p.Leu134Pro	missense_variant	4/5	5		ENSP00000420753.1
SPATA21	ENST00000466212.5	n.2723T>C		non_coding_transcript_exon_variant	15/17	2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 33

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

Feb 06, 2024

The c.1277T>C (p.L426P) alteration is located in exon 12 (coding exon 10) of the SPATA21 gene. This alteration results from a T to C substitution at nucleotide position 1277, causing the leucine (L) at amino acid position 426 to be replaced by a proline (P). 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	0.063
BayesDel_addAF	Pathogenic	0.23	D
BayesDel_noAF	Uncertain	0.090
CADD	Benign	15
DANN	Benign	0.43
DEOGEN2	Benign	0.094	.;T;.
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.19	N
LIST_S2	Benign	0.37	T;T;T
M_CAP	Benign	0.034	D
MetaRNN	Benign	0.14	T;T;T
MetaSVM	Benign	-0.80	T
MutationAssessor	Benign	1.7	.;L;.
PrimateAI	Benign	0.34	T
PROVEAN	Pathogenic	-4.8	D;D;D
REVEL	Uncertain	0.36
Sift	Uncertain	0.0060	D;D;D
Sift4G	Uncertain	0.0060	D;D;D
Polyphen		0.017	.;B;.
Vest4		0.79, 0.79
MutPred		0.35		.;Gain of loop (P = 0.0013);.;
MVP		0.092
MPC		0.17
ClinPred		0.60	D
GERP RS		3.7
Varity_R		0.32
gMVP		0.57

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.090		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: chr1-16725914;