2-200419320-G-T

Variant summary

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

The NM_001100423.2(SPATS2L):c.269G>T(p.Arg90Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000687 in 1,455,620 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: SPATS2L NM_001100423.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.74

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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SPATS2L	NM_001100423.2	c.269G>T	p.Arg90Met	missense_variant	6/13	ENST00000409140.8
LOC101927741	XR_007088047.1	n.911-7812C>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SPATS2L	ENST00000409140.8	c.269G>T	p.Arg90Met	missense_variant	6/13	2	NM_001100423.2	P1
	ENST00000655656.1	n.814+10103C>A		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.87e-7 AC: 1 AN: 1455620 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 723452

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000254

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

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

Mar 12, 2024

The c.269G>T (p.R90M) alteration is located in exon 6 (coding exon 4) of the SPATS2L gene. This alteration results from a G to T substitution at nucleotide position 269, causing the arginine (R) at amino acid position 90 to be replaced by a methionine (M). 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	0.12
BayesDel_addAF	Pathogenic	0.31	D
BayesDel_noAF	Benign	-0.22
Cadd	Benign	21
Dann	Benign	0.96
DEOGEN2	Benign	0.0093	T;T;T;T;T;T;T;.;T;T;T;T;T;.;.;.;.;.
Eigen	Uncertain	0.34
Eigen_PC	Uncertain	0.37
FATHMM_MKL	Uncertain	0.92	D
LIST_S2	Benign	0.80	T;.;.;.;T;T;.;T;T;T;T;T;T;T;T;T;T;T
M_CAP	Benign	0.014	T
MetaRNN	Uncertain	0.52	D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D
MetaSVM	Benign	-0.76	T
MutationTaster	Benign	0.70	D;D;D;D;D;D;D;D;D
PrimateAI	Benign	0.41	T
PROVEAN	Benign	-0.39	N;N;N;N;N;N;N;N;N;N;N;N;N;.;N;N;N;N
REVEL	Uncertain	0.32
Sift	Uncertain	0.010	D;D;D;D;D;D;D;D;T;T;T;D;T;.;D;D;T;T
Sift4G	Uncertain	0.049	D;T;T;T;T;T;T;T;T;T;T;T;T;T;.;T;T;T
Polyphen		0.99, 0.99	.;D;D;D;.;.;D;D;.;.;.;D;.;.;.;.;.;.
Vest4		0.43, 0.40, 0.42, 0.41, 0.41
MutPred		0.51		Loss of MoRF binding (P = 0.0522);Loss of MoRF binding (P = 0.0522);Loss of MoRF binding (P = 0.0522);Loss of MoRF binding (P = 0.0522);.;Loss of MoRF binding (P = 0.0522);Loss of MoRF binding (P = 0.0522);Loss of MoRF binding (P = 0.0522);Loss of MoRF binding (P = 0.0522);Loss of MoRF binding (P = 0.0522);Loss of MoRF binding (P = 0.0522);Loss of MoRF binding (P = 0.0522);Loss of MoRF binding (P = 0.0522);.;.;Loss of MoRF binding (P = 0.0522);Loss of MoRF binding (P = 0.0522);.;
MVP		0.12
MPC		0.96
ClinPred		0.76	D
GERP RS		4.6
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.076
gMVP		0.48

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: rs1359788128; hg19: chr2-201284043; COSMIC: COSV62353528;