Genetic Variant TAFA2:p.Leu49Val (chr12-61754986-G-C) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_178539.5(TAFA2):c.145C>G(p.Leu49Val) variant causes a missense change. The variant allele was found at a frequency of 0.000000685 in 1,460,740 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. L49F) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

TAFA2
NM_178539.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 4.01

Publications

1 publications found

Variant links:

Genes affected

TAFA2 (HGNC:21589): (TAFA chemokine like family member 2) This gene is a member of the TAFA family which is composed of five highly homologous genes that encode small secreted proteins. These proteins contain conserved cysteine residues at fixed positions, and are distantly related to MIP-1alpha, a member of the CC-chemokine family. The TAFA proteins are predominantly expressed in specific regions of the brain, and are postulated to function as brain-specific chemokines or neurokines, that act as regulators of immune and nervous cells. [provided by RefSeq, Jul 2008]

TAFA2 links:

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ACMG classification

Classification was made for transcript

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=0.09729645).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TAFA2	NM_178539.5 link	c.145C>G	p.Leu49Val	missense_variant	Exon 3 of 5	ENST00000416284.8	NP_848634.1	Q8N3H0-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TAFA2	ENST00000416284.8 link	c.145C>G	p.Leu49Val	missense_variant	Exon 3 of 5	1	NM_178539.5	ENSP00000393987.3		Q8N3H0-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000400

AC:

AN:

250248

AF XY:

0.00

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

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:

6.85e-7

AC:

AN:

1460740

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

726640

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33408

American (AMR)

AF:

0.00

AC:

AN:

44592

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26104

East Asian (EAS)

AF:

0.00

AC:

AN:

39570

South Asian (SAS)

AF:

0.0000116

AC:

AN:

86228

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53380

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5754

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1111378

Other (OTH)

AF:

0.00

AC:

AN:

60326

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.425

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ExAC

AF:

0.00000824

AC:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.12

BayesDel_noAF

Benign

-0.31

CADD

Benign

(source)

DANN

Benign

0.65

DEOGEN2

Benign

0.010

T;T;T;.;.

Eigen

Benign

0.041

Eigen_PC

Benign

0.22

FATHMM_MKL

Uncertain

0.87

LIST_S2

Benign

0.83

.;T;T;T;T

M_CAP

Benign

0.0051

MetaRNN

Benign

0.097

T;T;T;T;T

MetaSVM

Benign

-0.98

MutationAssessor

Benign

0.49

N;N;.;.;.

PhyloP100

4.0

PrimateAI

Uncertain

0.71

PROVEAN

Benign

0.72

N;N;N;N;N

REVEL

Benign

0.085

Sift

Benign

1.0

T;T;T;T;T

Sift4G

Benign

1.0

T;T;.;T;.

Polyphen

0.27

B;B;.;.;.

Vest4

0.46

MutPred

0.26

Gain of catalytic residue at V47 (P = 0.0046);Gain of catalytic residue at V47 (P = 0.0046);.;.;.;

MVP

0.068

MPC

0.60

ClinPred

0.13

GERP RS

5.4

Varity_R

0.21

gMVP

0.47

Mutation Taster

=84/16

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over