19-4652147-G-T

Variant names:

• chr19-4652147-G-T
• rs759851611
• NM_152362.3:c.278G>T

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_152362.3(TNFAIP8L1):​c.278G>T​(p.Arg93Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000708 in 1,411,640 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign 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. R93W) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 7.1e-7 (0 hom.)
• Consequence: TNFAIP8L1 NM_152362.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.19
• Publications: 0 publications found

Genes affected

TNFAIP8L1 (HGNC:28279): (TNF alpha induced protein 8 like 1) Enables identical protein binding activity. Predicted to be involved in negative regulation of TOR signaling. Predicted to be active in cytoplasm. [provided by Alliance of Genome Resources, Apr 2022]

MYDGF (HGNC:16948): (myeloid derived growth factor) The protein encoded by this gene was previously thought to support proliferation of lymphoid cells and was considered an interleukin. However, this activity has not been reproducible and the function of this protein is currently unknown. [provided by RefSeq, Jul 2008]

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.31874847).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_152362.3. 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
	TNFAIP8L1	NM_152362.3	MANE Select	c.278G>T	p.Arg93Leu	missense	Exon 2 of 2	NP_689575.2	Q8WVP5
	TNFAIP8L1	NM_001167942.1		c.278G>T	p.Arg93Leu	missense	Exon 2 of 2	NP_001161414.1	Q8WVP5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TNFAIP8L1	ENST00000327473.9	TSL:1 MANE Select	c.278G>T	p.Arg93Leu	missense	Exon 2 of 2	ENSP00000331827.3	Q8WVP5
	TNFAIP8L1	ENST00000536716.1	TSL:2	c.278G>T	p.Arg93Leu	missense	Exon 2 of 2	ENSP00000444215.1	Q8WVP5
	TNFAIP8L1	ENST00000883935.1		c.278G>T	p.Arg93Leu	missense	Exon 2 of 2	ENSP00000553994.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 7.08e-7 AC: 1 AN: 1411640 Hom.: 0 Cov.: 31 AF XY: 0.00000143 AC XY: 1 AN XY: 698040

African (AFR) AF: 0.00 AC: 0 AN: 32060

American (AMR) AF: 0.00 AC: 0 AN: 37486

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25306

East Asian (EAS) AF: 0.0000274 AC: 1 AN: 36528

South Asian (SAS) AF: 0.00 AC: 0 AN: 81132

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 47184

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5388

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1088110

Other (OTH) AF: 0.00 AC: 0 AN: 58446

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.20
BayesDel_addAF	Benign	-0.13	T
BayesDel_noAF	Benign	-0.43
CADD	Benign	17
DANN	Uncertain	0.99
DEOGEN2	Benign	0.27	T
Eigen	Benign	-0.66
Eigen_PC	Benign	-0.72
FATHMM_MKL	Benign	0.38	N
LIST_S2	Benign	0.50	T
M_CAP	Benign	0.022	T
MetaRNN	Benign	0.32	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.6	L
PhyloP100		2.2
PrimateAI	Uncertain	0.50	T
PROVEAN	Uncertain	-3.9	D
REVEL	Benign	0.051
Sift	Uncertain	0.0010	D
Sift4G	Uncertain	0.0020	D
Polyphen		0.35	B
Vest4		0.21
MutPred		0.71		Loss of MoRF binding (P = 0.028)
MVP		0.16
MPC		1.4
ClinPred		0.86	D
GERP RS		-0.87
Varity_R		0.43
gMVP		0.60
Mutation Taster		=94/6	polymorphism

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: rs759851611; hg19: chr19-4652159;