12-49484607-T-G

Variant names:

• chr12-49484607-T-G
• NM_023071.4:c.43T>G

Variant summary

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

The NM_023071.4(SPATS2):​c.43T>G​(p.Phe15Val) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 31)
• Consequence: SPATS2 NM_023071.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.03

Genes affected

SPATS2 (HGNC:18650): (spermatogenesis associated serine rich 2) Enables RNA binding activity. Located in cytosol. [provided by Alliance of Genome Resources, Apr 2022]

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 rank	MANE	Protein	UniProt
SPATS2	NM_023071.4	c.43T>G	p.Phe15Val	missense_variant	Exon 4 of 14	ENST00000552918.6	NP_075559.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SPATS2	ENST00000552918.6	c.43T>G	p.Phe15Val	missense_variant	Exon 4 of 14	2	NM_023071.4	ENSP00000447947.2

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 31

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Mar 02, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.43T>G (p.F15V) alteration is located in exon 4 (coding exon 2) of the SPATS2 gene. This alteration results from a T to G substitution at nucleotide position 43, causing the phenylalanine (F) at amino acid position 15 to be replaced by a valine (V). 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	Pathogenic	0.93
BayesDel_addAF	Pathogenic	0.46	D
BayesDel_noAF	Pathogenic	0.43
CADD	Pathogenic	27
DANN	Uncertain	0.99
DEOGEN2	Benign	0.15	.;T;T;T;.;T;T;.;T;T
Eigen	Uncertain	0.65
Eigen_PC	Uncertain	0.66
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.86	D;D;D;D;D;.;.;D;D;T
M_CAP	Benign	0.0087	T
MetaRNN	Uncertain	0.48	T;T;T;T;T;T;T;T;T;T
MetaSVM	Benign	-0.52	T
MutationAssessor	Uncertain	2.6	.;.;.;.;.;M;M;.;M;.
PrimateAI	Uncertain	0.75	T
PROVEAN	Uncertain	-2.9	D;D;D;D;D;N;N;D;N;D
REVEL	Uncertain	0.33
Sift	Uncertain	0.0040	D;D;D;D;D;D;D;D;D;D
Sift4G	Pathogenic	0.0	D;D;D;D;D;D;D;D;D;D
Polyphen		0.99	.;.;.;.;.;D;D;.;D;.
Vest4		0.85, 0.81
MutPred		0.27		Gain of MoRF binding (P = 0.1764);Gain of MoRF binding (P = 0.1764);Gain of MoRF binding (P = 0.1764);Gain of MoRF binding (P = 0.1764);Gain of MoRF binding (P = 0.1764);Gain of MoRF binding (P = 0.1764);Gain of MoRF binding (P = 0.1764);Gain of MoRF binding (P = 0.1764);Gain of MoRF binding (P = 0.1764);Gain of MoRF binding (P = 0.1764);
MVP		0.33
MPC		0.86
ClinPred		0.99	D
GERP RS		5.4
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.35
gMVP		0.69

Splicing

Name	Calibrated prediction	Score	Prediction
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: chr12-49878390;