chr1-16403728-T-C

Position:

• chr1-16403728-T-C

Variant summary

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

The NM_198546.1(SPATA21):​c.1000A>G​(p.Asn334Asp) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000274 in 1,460,038 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/23 in silico tools predict a benign outcome for this variant. 2/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. N334K) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 30)
  • Exomes 𝑓: 0.0000027 (0 hom.)
• Consequence: SPATA21 NM_198546.1 missense, splice_region
• Scores: Splicing: ADA: 0.9926
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.00

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=0.25652513).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SPATA21	NM_198546.1	c.1000A>G	p.Asn334Asp	missense_variant, splice_region_variant	10/13	ENST00000335496.5	NP_940948.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SPATA21	ENST00000335496.5	c.1000A>G	p.Asn334Asp	missense_variant, splice_region_variant	10/13	1	NM_198546.1	ENSP00000335612.1
SPATA21	ENST00000540400.1	c.931A>G	p.Asn311Asp	missense_variant, splice_region_variant	8/11	1		ENSP00000440046.1
SPATA21	ENST00000491418.5	c.124A>G	p.Asn42Asp	missense_variant, splice_region_variant	2/5	5		ENSP00000420753.1
SPATA21	ENST00000466212.5	n.2292A>G		splice_region_variant, non_coding_transcript_exon_variant	12/17	2

Frequencies

GnomAD3 genomes Cov.: 30

GnomAD4 exome AF: 0.00000274 AC: 4 AN: 1460038 Hom.: 0 Cov.: 30 AF XY: 0.00000275 AC XY: 2 AN XY: 726456

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000464

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 30

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

Jun 14, 2022

The c.1000A>G (p.N334D) alteration is located in exon 10 (coding exon 8) of the SPATA21 gene. This alteration results from a A to G substitution at nucleotide position 1000, causing the asparagine (N) at amino acid position 334 to be replaced by an aspartic acid (D). 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	0.13
BayesDel_addAF	Benign	-0.14	T
BayesDel_noAF	Benign	-0.44
CADD	Benign	22
DANN	Uncertain	1.0
DEOGEN2	Benign	0.012	.;T;.
Eigen	Benign	0.11
Eigen_PC	Benign	0.13
FATHMM_MKL	Benign	0.62	D
LIST_S2	Benign	0.58	T;T;T
M_CAP	Benign	0.021	T
MetaRNN	Benign	0.26	T;T;T
MetaSVM	Benign	-0.89	T
MutationAssessor	Benign	1.6	.;L;.
PrimateAI	Benign	0.40	T
PROVEAN	Uncertain	-3.2	D;D;D
REVEL	Benign	0.14
Sift	Benign	0.040	D;D;T
Sift4G	Uncertain	0.057	T;T;T
Polyphen		0.80	.;P;.
Vest4		0.21, 0.23
MutPred		0.37		.;Gain of ubiquitination at K339 (P = 0.0661);.;
MVP		0.53
MPC		0.11
ClinPred		0.92	D
GERP RS		3.7
Varity_R		0.20
gMVP		0.33

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Pathogenic	0.99
dbscSNV1_RF	Benign	0.63
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: chr1-16730223;