Variant 1-112726661-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The ENST00000369630.7(TAFA3):c.491G>A(p.Gly164Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000274 in 1,461,660 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/17 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000027 ( 0 hom. )

Consequence

TAFA3
ENST00000369630.7 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.14

Variant links:

Genes affected

TAFA3 (HGNC:21590): (TAFA chemokine like family member 3) 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. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene. [provided by RefSeq, Nov 2011]

TAFA3 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.09982017).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
TAFA3	NM_182759.3 linkuse as main transcript	c.*21G>A		3_prime_UTR_variant	6/6	ENST00000361886.4
TAFA3	NM_001004440.2 linkuse as main transcript	c.491G>A	p.Gly164Glu	missense_variant	6/6
TAFA3	NR_169586.1 linkuse as main transcript	n.914G>A		non_coding_transcript_exon_variant	6/6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TAFA3	ENST00000369630.7 linkuse as main transcript	c.491G>A	p.Gly164Glu	missense_variant	5/5	1			Q7Z5A8-2
TAFA3	ENST00000361886.4 linkuse as main transcript	c.*21G>A		3_prime_UTR_variant	6/6	1	NM_182759.3	P1	Q7Z5A8-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000398

AC:

AN:

251166

Hom.:

AF XY:

0.00000737

AC XY:

AN XY:

135740

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 SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.000163

GnomAD4 exome

AF:

0.00000274

AC:

AN:

1461660

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

727132

show subpopulations

Gnomad4 AFR exome

AF:

0.0000299

Gnomad4 AMR exome

AF:

0.0000224

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:

0.00000180

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Bravo

AF:

0.0000340

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Sep 12, 2023

The c.491G>A (p.G164E) alteration is located in exon 5 (coding exon 4) of the FAM19A3 gene. This alteration results from a G to A substitution at nucleotide position 491, causing the glycine (G) at amino acid position 164 to be replaced by a glutamic acid (E). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.24

BayesDel_noAF

Benign

-0.50

CADD

Benign

2.8

DANN

Benign

0.87

Eigen

Benign

-0.51

Eigen_PC

Benign

-0.62

FATHMM_MKL

Benign

0.052

LIST_S2

Benign

0.37

M_CAP

Benign

0.0040

MetaRNN

Benign

0.10

MetaSVM

Benign

-1.1

MutationTaster

Benign

1.0

N;N

PrimateAI

Benign

0.29

PROVEAN

Benign

0.060

REVEL

Benign

0.092

Sift

Uncertain

0.0070

Sift4G

Uncertain

0.0040

Polyphen

0.83

Vest4

0.053

MutPred

0.11

Gain of helix (P = 0.0164);

MVP

0.092

MPC

0.50

ClinPred

0.38

GERP RS

3.9

gMVP

0.049

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over