2-230444331-A-G

Position:

• chr2-230444331-A-G

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Moderate BP6_Moderate

The NM_001080391.2(SP100):​c.424A>G​(p.Lys142Glu) 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. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: SP100 NM_001080391.2 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.207

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 Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.13691577).
• BP6: Variant 2-230444331-A-G is Benign according to our data. Variant chr2-230444331-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 2265359.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SP100	NM_001080391.2	c.424A>G	p.Lys142Glu	missense_variant	4/29	ENST00000340126.9
LOC101928816	XR_427235.4	n.472-966T>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SP100	ENST00000340126.9	c.424A>G	p.Lys142Glu	missense_variant	4/29	1	NM_001080391.2	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 07, 2021

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Uncertain	0.061	T
BayesDel_noAF	Benign	-0.15
CADD	Benign	1.2
DANN	Benign	0.38
DEOGEN2	Uncertain	0.44	T;.;D;D;.;.;.;.
Eigen	Benign	-1.7
Eigen_PC	Benign	-1.9
FATHMM_MKL	Benign	0.0091	N
LIST_S2	Benign	0.56	T;T;T;T;T;T;T;T
M_CAP	Benign	0.049	D
MetaRNN	Benign	0.14	T;T;T;T;T;T;T;T
MetaSVM	Benign	-0.31	T
MutationAssessor	Benign	1.3	L;.;.;.;L;L;L;.
MutationTaster	Benign	1.0	N;N;N;N;N;N;N;N
PrimateAI	Benign	0.33	T
PROVEAN	Benign	-1.3	N;N;N;N;N;N;N;N
REVEL	Uncertain	0.34
Sift	Benign	0.17	T;T;T;T;.;T;T;T
Sift4G	Uncertain	0.043	D;T;T;T;T;T;T;.
Polyphen		0.019	B;.;.;B;B;.;B;.
Vest4		0.12
MutPred		0.55		Loss of methylation at K142 (P = 0.0071);.;.;.;Loss of methylation at K142 (P = 0.0071);Loss of methylation at K142 (P = 0.0071);Loss of methylation at K142 (P = 0.0071);.;
MVP		0.64
MPC		0.21
ClinPred		0.069	T
GERP RS		-7.2
Varity_R		0.16
gMVP		0.80

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: chr2-231309046;