19-4652132-G-A

Variant names:

• chr19-4652132-G-A
• rs778292073
• NM_152362.3:c.263G>A

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_152362.3(TNFAIP8L1):​c.263G>A​(p.Arg88Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000014 in 1,424,546 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: TNFAIP8L1 NM_152362.3 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.57

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

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.037484556).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TNFAIP8L1	NM_152362.3	c.263G>A	p.Arg88Gln	missense_variant	Exon 2 of 2	ENST00000327473.9	NP_689575.2
TNFAIP8L1	NM_001167942.1	c.263G>A	p.Arg88Gln	missense_variant	Exon 2 of 2		NP_001161414.1
TNFAIP8L1	XM_005259487.4	c.263G>A	p.Arg88Gln	missense_variant	Exon 2 of 2		XP_005259544.1
TNFAIP8L1	XM_011527680.3	c.263G>A	p.Arg88Gln	missense_variant	Exon 2 of 2		XP_011525982.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TNFAIP8L1	ENST00000327473.9	c.263G>A	p.Arg88Gln	missense_variant	Exon 2 of 2	1	NM_152362.3	ENSP00000331827.3
TNFAIP8L1	ENST00000536716.1	c.263G>A	p.Arg88Gln	missense_variant	Exon 2 of 2	2		ENSP00000444215.1
MYDGF	ENST00000599761.5	c.184+7799C>T		intron_variant	Intron 3 of 3	3		ENSP00000469136.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD3 exomes AF: 0.00000544 AC: 1 AN: 183700 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 99232

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000757

Gnomad SAS 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: 0.00000140 AC: 2 AN: 1424546 Hom.: 0 Cov.: 31 AF XY: 0.00000142 AC XY: 1 AN XY: 705490

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 9.14e-7

Gnomad4 OTH exome AF: 0.0000170

GnomAD4 genome Cov.: 33

Bravo AF: 0.00000378

ExAC AF: 0.00000847 AC: 1

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Feb 08, 2025

Ambry Genetics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.061
BayesDel_addAF	Benign	-0.38	T
BayesDel_noAF	Benign	-0.78
CADD	Benign	9.9
DANN	Benign	0.97
DEOGEN2	Benign	0.070	T;T
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.11	N
LIST_S2	Benign	0.10	.;T
M_CAP	Benign	0.015	T
MetaRNN	Benign	0.037	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-0.29	N;N
PrimateAI	Benign	0.41	T
PROVEAN	Benign	1.7	N;N
REVEL	Benign	0.032
Sift	Benign	0.29	T;T
Sift4G	Benign	0.57	T;T
Polyphen		0.0010	B;B
Vest4		0.044
MutPred		0.39		Loss of MoRF binding (P = 0.029);Loss of MoRF binding (P = 0.029);
MVP		0.040
MPC		1.1
ClinPred		0.058	T
GERP RS		-2.5
Varity_R		0.016
gMVP		0.099

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

LitVar

Other links and lift over

dbSNP: rs778292073; hg19: chr19-4652144;