NM_001100423.2:c.494A>C

Variant names:

• chr2-200439170-A-C
• rs553630178
• NM_001100423.2:c.494A>C

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_001100423.2(SPATS2L):​c.494A>C​(p.Lys165Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. K165R) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: SPATS2L NM_001100423.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.14
• Publications: 1 publications found

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

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SPATS2L	NM_001100423.2	c.494A>C	p.Lys165Thr	missense_variant	Exon 7 of 13	ENST00000409140.8	NP_001093893.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SPATS2L	ENST00000409140.8	c.494A>C	p.Lys165Thr	missense_variant	Exon 7 of 13	2	NM_001100423.2	ENSP00000386730.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000756

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.18
BayesDel_addAF	Uncertain	0.11	D
BayesDel_noAF	Uncertain	-0.070
CADD	Benign	20
DANN	Uncertain	1.0
DEOGEN2	Benign	0.091	T;T;T;T;T;T;T;.;.
Eigen	Uncertain	0.31
Eigen_PC	Uncertain	0.32
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Uncertain	0.87	.;.;.;D;.;D;D;D;D
M_CAP	Benign	0.016	T
MetaRNN	Uncertain	0.44	T;T;T;T;T;T;T;T;T
MetaSVM	Benign	-0.57	T
MutationAssessor	Benign	1.7	L;L;L;.;L;.;L;.;.
PhyloP100		2.1
PrimateAI	Uncertain	0.57	T
PROVEAN	Benign	-2.0	N;N;N;N;N;N;N;.;N
REVEL	Benign	0.25
Sift	Benign	0.038	D;D;D;D;D;D;D;.;D
Sift4G	Benign	0.23	T;T;T;T;T;D;T;T;.
Polyphen		0.95	P;P;P;.;P;.;P;.;.
Vest4		0.36
MutPred		0.58		Loss of ubiquitination at K165 (P = 1e-04);Loss of ubiquitination at K165 (P = 1e-04);Loss of ubiquitination at K165 (P = 1e-04);.;Loss of ubiquitination at K165 (P = 1e-04);Loss of ubiquitination at K165 (P = 1e-04);Loss of ubiquitination at K165 (P = 1e-04);.;.;
MVP		0.11
MPC		0.68
ClinPred		0.83	D
GERP RS		4.1
Varity_R		0.078
gMVP		0.64
Mutation Taster		=78/22	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs553630178; hg19: chr2-201303893;