2-200440714-G-A

Variant summary

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

The NM_001100423.2(SPATS2L):c.718G>A(p.Val240Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000144 in 1,461,366 control chromosomes in the GnomAD database, with no homozygous occurrence. 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)
  • Exomes 𝑓: 0.000014 (0 hom.)
• Consequence: SPATS2L NM_001100423.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.95

Genes affected

SPATS2L (HGNC:24574): (spermatogenesis associated serine rich 2 like) Enables RNA binding activity. Located in cytosol; nucleolus; and nucleoplasm. Part of protein-containing complex. [provided by Alliance of Genome Resources, Apr 2022]

(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=0.24726713).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SPATS2L	NM_001100423.2	c.718G>A	p.Val240Ile	missense_variant	8/13	ENST00000409140.8
LOC101927741	XR_007088047.1	n.662+8662C>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SPATS2L	ENST00000409140.8	c.718G>A	p.Val240Ile	missense_variant	8/13	2	NM_001100423.2	P1
	ENST00000655656.1	n.567-9177C>T		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.0000121 AC: 3 AN: 248838 Hom.: 0 AF XY: 0.0000148 AC XY: 2 AN XY: 134960

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000580

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000887

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000144 AC: 21 AN: 1461366 Hom.: 0 Cov.: 30 AF XY: 0.0000220 AC XY: 16 AN XY: 726960

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.0000447

Gnomad4 ASJ exome AF: 0.0000383

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000348

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000117

Gnomad4 OTH exome AF: 0.0000166

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000378

ExAC AF: 0.0000248 AC: 3

EpiCase AF: 0.0000546

EpiControl AF: 0.00

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 08, 2022

The c.718G>A (p.V240I) alteration is located in exon 8 (coding exon 6) of the SPATS2L gene. This alteration results from a G to A substitution at nucleotide position 718, causing the valine (V) at amino acid position 240 to be replaced by an isoleucine (I). 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	0.087
BayesDel_addAF	Benign	-0.26	T
BayesDel_noAF	Benign	-0.43
Cadd	Uncertain	24
Dann	Uncertain	1.0
DEOGEN2	Benign	0.011	T;T;T;T;T;.;T;T;T;.;.;.;.
Eigen	Uncertain	0.27
Eigen_PC	Uncertain	0.38
FATHMM_MKL	Benign	0.75	D
M_CAP	Benign	0.0045	T
MetaRNN	Benign	0.25	T;T;T;T;T;T;T;T;T;T;T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.2	L;L;L;.;L;.;.;L;.;.;.;.;.
MutationTaster	Benign	0.93	N;N;N;N;N;N;N;N;N
PrimateAI	Uncertain	0.64	T
PROVEAN	Benign	-0.61	N;N;N;N;N;N;N;N;N;.;N;N;N
REVEL	Benign	0.10
Sift	Benign	0.12	T;T;T;T;T;T;T;T;T;.;T;T;T
Sift4G	Benign	0.47	T;T;T;T;T;T;T;T;T;T;.;T;T
Polyphen		0.72	P;P;P;.;P;D;.;P;.;.;.;.;.
Vest4		0.17
MutPred		0.68		Loss of sheet (P = 0.0315);Loss of sheet (P = 0.0315);Loss of sheet (P = 0.0315);.;Loss of sheet (P = 0.0315);.;.;Loss of sheet (P = 0.0315);.;.;.;.;.;
MVP		0.082
MPC		0.23
ClinPred		0.47	T
GERP RS		5.1
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.046
gMVP		0.78

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

LitVar

Other links and lift over

dbSNP: rs765351636; hg19: chr2-201305437;