17-28339639-T-G

Variant names:

• chr17-28339639-T-G
• rs782766421
• NM_021137.5:c.118T>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.118T>G​(p.Tyr40Asp) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. Y40H) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: TNFAIP1 NM_021137.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.67
• 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: MetaRNN computational evidence supports a deleterious effect, 0.885

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.118T>G	p.Tyr40Asp	missense	Exon 2 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.118T>G	p.Tyr40Asp	missense	Exon 2 of 7	ENSP00000226225.2	Q13829-1
	TNFAIP1	ENST00000902207.1		c.118T>G	p.Tyr40Asp	missense	Exon 3 of 8	ENSP00000572266.1
	TNFAIP1	ENST00000902210.1		c.118T>G	p.Tyr40Asp	missense	Exon 3 of 8	ENSP00000572269.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00000400 AC: 1 AN: 250244 AF XY: 0.00000739

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000544

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ExAC AF: 0.00000824 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.80
BayesDel_addAF	Pathogenic	0.26	D
BayesDel_noAF	Pathogenic	0.30
CADD	Pathogenic	31
DANN	Benign	0.95
DEOGEN2	Uncertain	0.65	D
Eigen	Pathogenic	0.72
Eigen_PC	Pathogenic	0.68
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.90	D
M_CAP	Uncertain	0.21	D
MetaRNN	Pathogenic	0.89	D
MetaSVM	Uncertain	0.17	D
MutationAssessor	Uncertain	2.4	M
PhyloP100		7.7
PrimateAI	Pathogenic	0.83	D
PROVEAN	Pathogenic	-8.0	D
REVEL	Pathogenic	0.78
Sift	Uncertain	0.025	D
Sift4G	Benign	0.33	T
Polyphen		1.0	D
Vest4		0.85
MutPred		0.55		Gain of helix (P = 0.0696)
MVP		0.89
MPC		1.8
ClinPred		0.99	D
GERP RS		5.7
Varity_R		0.86
gMVP		0.75

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

Other links and lift over

dbSNP: rs782766421; hg19: chr17-26666665;