Variant 22-48646720-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001082967.3(TAFA5):c.236C>T(p.Thr79Met) variant causes a missense change. The variant allele was found at a frequency of 0.000051 in 1,589,314 control chromosomes in the GnomAD database, including 1 homozygotes. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000059 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000050 ( 1 hom. )

Consequence

TAFA5
NM_001082967.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.18

Variant links:

Genes affected

TAFA5 (HGNC:21592): (TAFA chemokine like family member 5) 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, Sep 2013]

TAFA5 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TAFA5	NM_001082967.3 linkuse as main transcript	c.236C>T	p.Thr79Met	missense_variant	2/4	ENST00000402357.6
TAFA5	NM_015381.7 linkuse as main transcript	c.215C>T	p.Thr72Met	missense_variant	2/4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TAFA5	ENST00000402357.6 linkuse as main transcript	c.236C>T	p.Thr79Met	missense_variant	2/4	1	NM_001082967.3	P4	Q7Z5A7-1
TAFA5	ENST00000336769.9 linkuse as main transcript	c.236C>T	p.Thr79Met	missense_variant	2/4	4
TAFA5	ENST00000358295.9 linkuse as main transcript	c.215C>T	p.Thr72Met	missense_variant	2/4	2		A1	Q7Z5A7-2
TAFA5	ENST00000473898.1 linkuse as main transcript	n.120-60997C>T		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes

AF:

0.0000592

AC:

AN:

152144

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000131

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000882

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000632

AC:

AN:

205714

Hom.:

AF XY:

0.0000790

AC XY:

AN XY:

113934

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000130

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000142

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000554

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000501

AC:

AN:

1437170

Hom.:

Cov.:

AF XY:

0.0000644

AC XY:

AN XY:

714164

show subpopulations

Gnomad4 AFR exome

AF:

0.0000301

Gnomad4 AMR exome

AF:

0.000119

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000257

Gnomad4 SAS exome

AF:

0.000189

Gnomad4 FIN exome

AF:

0.0000225

Gnomad4 NFE exome

AF:

0.0000399

Gnomad4 OTH exome

AF:

0.0000671

GnomAD4 genome

AF:

0.0000592

AC:

AN:

152144

Hom.:

Cov.:

AF XY:

0.0000673

AC XY:

AN XY:

74310

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.000131

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000882

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000453

Hom.:

Bravo

AF:

0.0000718

ExAC

AF:

0.0000422

AC:

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

Jun 03, 2022

The c.236C>T (p.T79M) alteration is located in exon 2 (coding exon 2) of the FAM19A5 gene. This alteration results from a C to T substitution at nucleotide position 236, causing the threonine (T) at amino acid position 79 to be replaced by a methionine (M). 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

AlphaMissense

Uncertain

0.47

BayesDel_addAF

Pathogenic

0.26

BayesDel_noAF

Pathogenic

0.38

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Benign

0.37

T;.;.

Eigen

Pathogenic

0.78

Eigen_PC

Pathogenic

0.74

FATHMM_MKL

Uncertain

0.92

LIST_S2

Uncertain

0.95

D;D;D

M_CAP

Uncertain

0.28

MetaRNN

Uncertain

0.69

D;D;D

MetaSVM

Uncertain

-0.026

MutationAssessor

Uncertain

2.4

M;.;.

MutationTaster

Benign

1.0

D;D

PrimateAI

Pathogenic

0.88

PROVEAN

Pathogenic

-5.9

D;D;D

REVEL

Uncertain

0.44

Sift

Pathogenic

0.0

D;D;D

Sift4G

Pathogenic

0.0

D;D;D

Polyphen

1.0

D;.;D

Vest4

0.78

MutPred

0.52

Loss of phosphorylation at T79 (P = 0.0398);Loss of phosphorylation at T79 (P = 0.0398);.;

MVP

0.17

MPC

1.7

ClinPred

0.65

GERP RS

5.2

Varity_R

0.58

gMVP

0.79

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