chr15-51105005-C-G

Position:

• chr15-51105005-C-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP6_Very_Strong BS2

The ENST00000327536.5(TNFAIP8L3):​c.172G>C​(p.Ala58Pro) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00605 in 1,614,156 control chromosomes in the GnomAD database, including 40 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/23 in silico tools predict a benign outcome for this variant. 2/3 splice prediction tools predicting alterations to normal splicing. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0042 (3 hom., cov: 32)
  • Exomes 𝑓: 0.0062 (37 hom.)
• Consequence: TNFAIP8L3 ENST00000327536.5 missense, splice_region
• Scores: Splicing: ADA: 1.000
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.0760

Genes affected

TNFAIP8L3 (HGNC:20620): (TNF alpha induced protein 8 like 3) Predicted to enable phosphatidylinositol binding activity and phosphatidylinositol transfer activity. Predicted to be involved in several processes, including inositol lipid-mediated signaling; positive regulation of intracellular signal transduction; and positive regulation of phosphatidylinositol 3-kinase activity. Located in cytosol and nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

MIR4713HG (HGNC:53124): (MIR4713 host gene)

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP6: Variant 15-51105005-C-G is Benign according to our data. Variant chr15-51105005-C-G is described in ClinVar as [Likely_benign]. Clinvar id is 719370.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS2: High Homozygotes in GnomAd4 at 3 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MIR4713HG	NR_146310.1	n.194+67324C>G		intron_variant, non_coding_transcript_variant
TNFAIP8L3	NM_207381.4	c.172G>C	p.Ala58Pro	missense_variant, splice_region_variant	1/3		NP_997264.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TNFAIP8L3	ENST00000327536.5	c.172G>C	p.Ala58Pro	missense_variant, splice_region_variant	1/3	1		ENSP00000328016
MIR4713HG	ENST00000559909.1	n.194+67324C>G		intron_variant, non_coding_transcript_variant		4

Frequencies

GnomAD3 genomes AF: 0.00416 AC: 633 AN: 152196 Hom.: 3 Cov.: 32

Gnomad AFR AF: 0.00118

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00203

Gnomad ASJ AF: 0.000865

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00367

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00741

Gnomad OTH AF: 0.00287

GnomAD3 exomes AF: 0.00344 AC: 862 AN: 250752 Hom.: 2 AF XY: 0.00350 AC XY: 474 AN XY: 135616

Gnomad AFR exome AF: 0.00105

Gnomad AMR exome AF: 0.000809

Gnomad ASJ exome AF: 0.000992

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000719

Gnomad FIN exome AF: 0.00379

Gnomad NFE exome AF: 0.00608

Gnomad OTH exome AF: 0.00261

GnomAD4 exome AF: 0.00625 AC: 9136 AN: 1461842 Hom.: 37 Cov.: 31 AF XY: 0.00604 AC XY: 4393 AN XY: 727214

Gnomad4 AFR exome AF: 0.000896

Gnomad4 AMR exome AF: 0.000850

Gnomad4 ASJ exome AF: 0.00122

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000754

Gnomad4 FIN exome AF: 0.00464

Gnomad4 NFE exome AF: 0.00764

Gnomad4 OTH exome AF: 0.00366

GnomAD4 genome AF: 0.00416 AC: 633 AN: 152314 Hom.: 3 Cov.: 32 AF XY: 0.00381 AC XY: 284 AN XY: 74472

Gnomad4 AFR AF: 0.00118

Gnomad4 AMR AF: 0.00203

Gnomad4 ASJ AF: 0.000865

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000207

Gnomad4 FIN AF: 0.00367

Gnomad4 NFE AF: 0.00741

Gnomad4 OTH AF: 0.00284

Alfa AF: 0.00568 Hom.: 2

Bravo AF: 0.00381

TwinsUK AF: 0.00863 AC: 32

ALSPAC AF: 0.00752 AC: 29

ESP6500AA AF: 0.00228 AC: 10

ESP6500EA AF: 0.00815 AC: 70

ExAC AF: 0.00324 AC: 393

Asia WGS AF: 0.000289 AC: 1 AN: 3478

EpiCase AF: 0.00545

EpiControl AF: 0.00456

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Likely benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Apr 10, 2018	- -
Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.085
BayesDel_addAF	Benign	-0.54	T
BayesDel_noAF	Benign	-0.55
CADD	Benign	16
DANN	Benign	0.97
DEOGEN2	Benign	0.052	T
Eigen	Benign	-0.84
Eigen_PC	Benign	-0.91
FATHMM_MKL	Benign	0.032	N
LIST_S2	Benign	0.26	T
M_CAP	Benign	0.010	T
MetaRNN	Benign	0.0033	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.0	N
MutationTaster	Benign	1.0	N
PrimateAI	Benign	0.43	T
PROVEAN	Benign	0.27	N
REVEL	Benign	0.0070
Sift	Benign	0.062	T
Sift4G	Benign	0.12	T
Polyphen		0.49	P
Vest4		0.23
MVP		0.17
MPC		0.31
ClinPred		0.0074	T
GERP RS		1.7
Varity_R		0.11
gMVP		0.055

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Pathogenic	1.0
dbscSNV1_RF	Pathogenic	0.97
SpliceAI score (max)		0.050		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: rs150980610; hg19: chr15-51397202;