1-151158739-G-C

Position:

• chr1-151158739-G-C

Variant summary

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

The NM_024575.5(TNFAIP8L2):​c.42G>C​(p.Glu14Asp) variant causes a missense change involving the alteration of a 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: 31)
• Consequence: TNFAIP8L2 NM_024575.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 10.0

Genes affected

TNFAIP8L2 (HGNC:26277): (TNF alpha induced protein 8 like 2) Predicted to be involved in negative regulation of T cell activation and negative regulation of inflammatory response. Predicted to be active in cytoplasm. [provided by Alliance of Genome Resources, Apr 2022]

TNFAIP8L2-SCNM1 (HGNC:):

SCNM1 (HGNC:23136): (sodium channel modifier 1) SCNM1 is a zinc finger protein and putative splicing factor. In mice, Scnm1 modifies phenotypic expression of Scn8a (MIM 600702) mutations (Buchner et al., 2003 [PubMed 12920299]).[supplied by OMIM, Oct 2009]

LYSMD1 (HGNC:32070): (LysM domain containing 1) Located in nucleoplasm. [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/exons	MANE	Protein	UniProt
TNFAIP8L2	NM_024575.5	c.42G>C	p.Glu14Asp	missense_variant	2/2	ENST00000368910.4	NP_078851.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TNFAIP8L2	ENST00000368910.4	c.42G>C	p.Glu14Asp	missense_variant	2/2	1	NM_024575.5	ENSP00000357906.3
SCNM1	ENST00000602841.5	c.-55+2017G>C		intron_variant		3		ENSP00000473282.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 31

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

Aug 12, 2021

The c.42G>C (p.E14D) alteration is located in exon 2 (coding exon 1) of the TNFAIP8L2 gene. This alteration results from a G to C substitution at nucleotide position 42, causing the glutamic acid (E) at amino acid position 14 to be replaced by an aspartic acid (D). 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	0.82
BayesDel_addAF	Benign	-0.091	T
BayesDel_noAF	Benign	-0.37
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.30	T
Eigen	Uncertain	0.44
Eigen_PC	Uncertain	0.49
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.95	D
M_CAP	Benign	0.011	T
MetaRNN	Uncertain	0.43	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.5	L
PrimateAI	Uncertain	0.55	T
PROVEAN	Benign	-1.9	N
REVEL	Benign	0.28
Sift	Uncertain	0.0030	D
Sift4G	Uncertain	0.0080	D
Polyphen		0.80	P
Vest4		0.28
MutPred		0.69		Loss of methylation at K15 (P = 0.0774);
MVP		0.17
MPC		0.86
ClinPred		0.96	D
GERP RS		3.8
Varity_R		0.49
gMVP		0.33

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: chr1-151131215;