2-200419437-C-T

Position:

• chr2-200419437-C-T

Variant summary

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

The NM_001100423.2(SPATS2L):​c.386C>T​(p.Pro129Leu) 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. 14/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: SPATS2L NM_001100423.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.52

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]

ENSG00000287299 (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=0.1223858).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SPATS2L	NM_001100423.2	c.386C>T	p.Pro129Leu	missense_variant	6/13	ENST00000409140.8	NP_001093893.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SPATS2L	ENST00000409140.8	c.386C>T	p.Pro129Leu	missense_variant	6/13	2	NM_001100423.2	ENSP00000386730.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

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

Dec 03, 2024

The c.386C>T (p.P129L) alteration is located in exon 6 (coding exon 4) of the SPATS2L gene. This alteration results from a C to T substitution at nucleotide position 386, causing the proline (P) at amino acid position 129 to be replaced by a leucine (L). 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	0.084
BayesDel_addAF	Benign	-0.079	T
BayesDel_noAF	Benign	-0.35
CADD	Benign	16
DANN	Benign	0.96
DEOGEN2	Benign	0.031	T;T;T;T;T;.;T;T;T;T;T;.;.;.;.;.
Eigen	Benign	-0.58
Eigen_PC	Benign	-0.52
FATHMM_MKL	Benign	0.29	N
LIST_S2	Benign	0.84	.;.;.;T;.;T;T;T;T;T;T;T;T;T;T;T
M_CAP	Benign	0.0093	T
MetaRNN	Benign	0.12	T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	1.5	L;L;L;.;L;L;.;.;.;L;.;.;.;.;.;.
PrimateAI	Benign	0.35	T
PROVEAN	Benign	-2.1	N;N;N;N;N;D;N;N;D;N;D;.;N;N;N;D
REVEL	Benign	0.030
Sift	Benign	0.042	D;D;D;D;D;D;T;T;T;D;D;.;D;T;T;D
Sift4G	Uncertain	0.053	T;T;T;T;T;D;D;D;D;T;D;D;.;D;D;D
Polyphen		0.0030	B;B;B;.;B;B;.;.;.;B;.;.;.;.;.;.
Vest4		0.18
MutPred		0.41		Gain of helix (P = 0.0117);Gain of helix (P = 0.0117);Gain of helix (P = 0.0117);.;Gain of helix (P = 0.0117);Gain of helix (P = 0.0117);Gain of helix (P = 0.0117);Gain of helix (P = 0.0117);Gain of helix (P = 0.0117);Gain of helix (P = 0.0117);Gain of helix (P = 0.0117);.;.;Gain of helix (P = 0.0117);Gain of helix (P = 0.0117);.;
MVP		0.068
MPC		0.28
ClinPred		0.33	T
GERP RS		3.6
Varity_R		0.051
gMVP		0.59

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr2-201284160;