NM_152362.3:c.442G>A

Variant names:

• chr19-4652311-G-A
• rs376296732
• NM_152362.3:c.442G>A

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_152362.3(TNFAIP8L1):​c.442G>A​(p.Gly148Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000833 in 1,560,534 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 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. G148C) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.0000066 (0 hom., cov: 33)
  • Exomes 𝑓: 0.0000085 (0 hom.)
• Consequence: TNFAIP8L1 NM_152362.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.823
• 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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.12365216).

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.442G>A	p.Gly148Ser	missense	Exon 2 of 2	NP_689575.2	Q8WVP5
	TNFAIP8L1	NM_001167942.1		c.442G>A	p.Gly148Ser	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.442G>A	p.Gly148Ser	missense	Exon 2 of 2	ENSP00000331827.3	Q8WVP5
	TNFAIP8L1	ENST00000536716.1	TSL:2	c.442G>A	p.Gly148Ser	missense	Exon 2 of 2	ENSP00000444215.1	Q8WVP5
	TNFAIP8L1	ENST00000883935.1		c.442G>A	p.Gly148Ser	missense	Exon 2 of 2	ENSP00000553994.1

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152250 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.0000241

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.00000629 AC: 1 AN: 158902 AF XY: 0.0000115

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000369

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000852 AC: 12 AN: 1408284 Hom.: 0 Cov.: 31 AF XY: 0.00000861 AC XY: 6 AN XY: 696886

African (AFR) AF: 0.000156 AC: 5 AN: 31962

American (AMR) AF: 0.0000259 AC: 1 AN: 38570

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

East Asian (EAS) AF: 0.0000274 AC: 1 AN: 36432

South Asian (SAS) AF: 0.0000124 AC: 1 AN: 80724

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 44200

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5722

European-Non Finnish (NFE) AF: 0.00000368 AC: 4 AN: 1086998

Other (OTH) AF: 0.00 AC: 0 AN: 58370

GnomAD4 genome AF: 0.00000657 AC: 1 AN: 152250 Hom.: 0 Cov.: 33 AF XY: 0.0000134 AC XY: 1 AN XY: 74378

African (AFR) AF: 0.0000241 AC: 1 AN: 41470

American (AMR) AF: 0.00 AC: 0 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5200

South Asian (SAS) AF: 0.00 AC: 0 AN: 4834

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10628

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 314

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68038

Other (OTH) AF: 0.00 AC: 0 AN: 2092

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000227

ESP6500AA AF: 0.000471 AC: 2

ESP6500EA AF: 0.00 AC: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.078
BayesDel_addAF	Benign	-0.29	T
BayesDel_noAF	Benign	-0.65
CADD	Benign	15
DANN	Uncertain	0.98
DEOGEN2	Benign	0.071	T
Eigen	Benign	-0.63
Eigen_PC	Benign	-0.52
FATHMM_MKL	Benign	0.30	N
LIST_S2	Uncertain	0.89	D
M_CAP	Benign	0.0086	T
MetaRNN	Benign	0.12	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.46	N
PhyloP100		0.82
PrimateAI	Uncertain	0.54	T
PROVEAN	Benign	0.61	N
REVEL	Benign	0.022
Sift	Benign	0.17	T
Sift4G	Benign	0.092	T
Polyphen		0.0020	B
Vest4		0.050
MVP		0.061
MPC		0.93
ClinPred		0.24	T
GERP RS		-1.3
Varity_R		0.040
gMVP		0.24
Mutation Taster		=79/21	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: rs376296732; hg19: chr19-4652323; COSMIC: COSV59420535; COSMIC: COSV59420535;