1-16400753-T-A

Position:

• chr1-16400753-T-A

Variant summary

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

The NM_198546.1(SPATA21):​c.1141A>T​(p.Ser381Cys) 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: SPATA21 NM_198546.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.96

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=0.2581041).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SPATA21	NM_198546.1	c.1141A>T	p.Ser381Cys	missense_variant	11/13	ENST00000335496.5	NP_940948.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SPATA21	ENST00000335496.5	c.1141A>T	p.Ser381Cys	missense_variant	11/13	1	NM_198546.1	ENSP00000335612.1
SPATA21	ENST00000540400.1	c.1072A>T	p.Ser358Cys	missense_variant	9/11	1		ENSP00000440046.1
SPATA21	ENST00000491418.5	c.265A>T	p.Ser89Cys	missense_variant	3/5	5		ENSP00000420753.1
SPATA21	ENST00000466212.5	n.2433A>T		non_coding_transcript_exon_variant	13/17	2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 33

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

Mar 06, 2023

The c.1141A>T (p.S381C) alteration is located in exon 11 (coding exon 9) of the SPATA21 gene. This alteration results from a A to T substitution at nucleotide position 1141, causing the serine (S) at amino acid position 381 to be replaced by a cysteine (C). 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	0.096
BayesDel_addAF	Benign	-0.0070	T
BayesDel_noAF	Benign	-0.25
CADD	Benign	21
DANN	Uncertain	0.98
DEOGEN2	Benign	0.012	.;T;.
Eigen	Benign	-0.076
Eigen_PC	Benign	-0.11
FATHMM_MKL	Benign	0.72	D
LIST_S2	Benign	0.68	T;T;T
M_CAP	Benign	0.050	D
MetaRNN	Benign	0.26	T;T;T
MetaSVM	Benign	-0.86	T
MutationAssessor	Benign	1.4	.;L;.
PrimateAI	Benign	0.36	T
PROVEAN	Uncertain	-3.2	D;D;D
REVEL	Benign	0.17
Sift	Uncertain	0.0060	D;D;D
Sift4G	Uncertain	0.019	D;D;D
Polyphen		0.98	.;D;.
Vest4		0.23, 0.30
MutPred		0.37		.;Loss of helix (P = 0.0444);.;
MVP		0.45
MPC		0.39
ClinPred		0.97	D
GERP RS		1.6
Varity_R		0.20
gMVP		0.23

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: chr1-16727248;