17-28342346-C-G

Variant names:

• chr17-28342346-C-G
• rs3093722
• NM_021137.5:c.618C>G

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_021137.5(TNFAIP1):​c.618C>G​(p.Asp206Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000687 in 1,455,274 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. D206D) has been classified as Benign.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: TNFAIP1 NM_021137.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.83
• Publications: 0 publications found

Genes affected

TNFAIP1 (HGNC:11894): (TNF alpha induced protein 1) This gene was identified as a gene whose expression can be induced by the tumor necrosis factor alpha (TNF) in umbilical vein endothelial cells. Studies of a similar gene in mouse suggest that the expression of this gene is developmentally regulated in a tissue-specific manner. [provided by RefSeq, Jul 2008]

ACMG classification

Our verdict: Uncertain_significance. The variant received 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: Splicing predictors support a deleterious effect. Scorers claiming Pathogenic: max_spliceai. No scorers claiming Uncertain. No scorers claiming Benign.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_021137.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TNFAIP1	NM_021137.5	MANE Select	c.618C>G	p.Asp206Glu	missense	Exon 6 of 7	NP_066960.1	Q13829-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TNFAIP1	ENST00000226225.7	TSL:1 MANE Select	c.618C>G	p.Asp206Glu	missense	Exon 6 of 7	ENSP00000226225.2	Q13829-1
	TNFAIP1	ENST00000902207.1		c.618C>G	p.Asp206Glu	missense	Exon 7 of 8	ENSP00000572266.1
	TNFAIP1	ENST00000902210.1		c.618C>G	p.Asp206Glu	missense	Exon 7 of 8	ENSP00000572269.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.87e-7 AC: 1 AN: 1455274 Hom.: 0 Cov.: 33 AF XY: 0.00000138 AC XY: 1 AN XY: 722698

African (AFR) AF: 0.00 AC: 0 AN: 33392

American (AMR) AF: 0.00 AC: 0 AN: 44652

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26062

East Asian (EAS) AF: 0.00 AC: 0 AN: 39464

South Asian (SAS) AF: 0.00 AC: 0 AN: 86068

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53354

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5750

European-Non Finnish (NFE) AF: 9.04e-7 AC: 1 AN: 1106458

Other (OTH) AF: 0.00 AC: 0 AN: 60074

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.58
BayesDel_addAF	Benign	0.0056	T
BayesDel_noAF	Benign	-0.23
CADD	Benign	17
DANN	Uncertain	0.98
DEOGEN2	Benign	0.15	T
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.26	N
LIST_S2	Uncertain	0.92	D
M_CAP	Benign	0.036	D
MetaRNN	Benign	0.13	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.7	L
PhyloP100		-1.8
PrimateAI	Pathogenic	0.87	D
PROVEAN	Benign	-1.2	N
REVEL	Benign	0.23
Sift	Benign	0.20	T
Sift4G	Benign	0.35	T
Polyphen		0.11	B
Vest4		0.62
MutPred		0.52		Gain of solvent accessibility (P = 0.0854)
MVP		0.13
MPC		0.69
ClinPred		0.56	D
GERP RS		-3.9
Varity_R		0.14
gMVP		0.68

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.85		Details are displayed if max score is > 0.2
DS_DG_spliceai		0.85		Position offset: -5

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

Other links and lift over

dbSNP: rs3093722; hg19: chr17-26669372;