2-230443038-A-C

Position:

• chr2-230443038-A-C

Variant summary

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

The NM_001080391.2(SP100):​c.209A>C​(p.Lys70Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: SP100 NM_001080391.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.102

Genes affected

SP100 (HGNC:11206): (SP100 nuclear antigen) This gene encodes a subnuclear organelle and major component of the PML (promyelocytic leukemia)-SP100 nuclear bodies. PML and SP100 are covalently modified by the SUMO-1 modifier, which is considered crucial to nuclear body interactions. The encoded protein binds heterochromatin proteins and is thought to play a role in tumorigenesis, immunity, and gene regulation. Alternatively spliced variants have been identified for this gene; one of which encodes a high-mobility group protein. [provided by RefSeq, Aug 2011]

LOC101928816 (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	Protein	UniProt
SP100	NM_001080391.2	c.209A>C	p.Lys70Thr	missense_variant	3/29	ENST00000340126.9	NP_001073860.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SP100	ENST00000340126.9	c.209A>C	p.Lys70Thr	missense_variant	3/29	1	NM_001080391.2	ENSP00000343023.4

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

Sep 26, 2022

The c.209A>C (p.K70T) alteration is located in exon 3 (coding exon 3) of the SP100 gene. This alteration results from a A to C substitution at nucleotide position 209, causing the lysine (K) at amino acid position 70 to be replaced by a threonine (T). 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	0.61
BayesDel_addAF	Uncertain	0.16	D
BayesDel_noAF	Uncertain	-0.010
CADD	Benign	18
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.68	D;.;D;D;.;.;.;.
Eigen	Benign	-0.19
Eigen_PC	Benign	-0.45
FATHMM_MKL	Benign	0.017	N
LIST_S2	Benign	0.79	T;T;T;T;T;T;T;T
M_CAP	Uncertain	0.088	D
MetaRNN	Uncertain	0.53	D;D;D;D;D;D;D;D
MetaSVM	Uncertain	0.29	D
MutationAssessor	Pathogenic	3.1	M;.;.;.;M;M;M;.
PrimateAI	Uncertain	0.55	T
PROVEAN	Uncertain	-3.0	D;D;D;D;D;D;D;D
REVEL	Uncertain	0.40
Sift	Uncertain	0.0010	D;D;D;D;.;D;D;D
Sift4G	Uncertain	0.0020	D;D;D;D;D;D;D;.
Polyphen		1.0	D;.;.;D;D;.;D;.
Vest4		0.34
MutPred		0.56		Loss of methylation at K70 (P = 0.011);.;.;.;Loss of methylation at K70 (P = 0.011);Loss of methylation at K70 (P = 0.011);Loss of methylation at K70 (P = 0.011);.;
MVP		0.92
MPC		0.45
ClinPred		0.94	D
GERP RS		-1.6
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.33
gMVP		0.55

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: chr2-231307753;