Variant 3-68006639-T-C details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_213609.4(TAFA1):c.13T>C(p.Ser5Pro) variant causes a missense change. The variant allele was found at a frequency of 0.00000137 in 1,461,144 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts 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: 32)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

TAFA1
NM_213609.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.73

Variant links:

Genes affected

TAFA1 (HGNC:21587): (TAFA chemokine like family member 1) 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]

TAFA1 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=0.23839143).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TAFA1	NM_213609.4 linkuse as main transcript	c.13T>C	p.Ser5Pro	missense_variant	2/5	ENST00000478136.6	NP_998774.2	Q7Z5A9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TAFA1	ENST00000478136.6 linkuse as main transcript	c.13T>C	p.Ser5Pro	missense_variant	2/5	1	NM_213609.4	ENSP00000418575.1		Q7Z5A9
TAFA1	ENST00000496687.1 linkuse as main transcript	c.13T>C	p.Ser5Pro	missense_variant	1/4	1		ENSP00000417496.1		Q7Z5A9

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000401

AC:

AN:

249272

Hom.:

AF XY:

0.00000740

AC XY:

AN XY:

135226

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:

0.00000885

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000137

AC:

AN:

1461144

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

726936

show subpopulations

Gnomad4 AFR exome

AF:

0.0000299

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:

9.00e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ExAC

AF:

0.00000826

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

Oct 12, 2024

The c.13T>C (p.S5P) alteration is located in exon 2 (coding exon 1) of the FAM19A1 gene. This alteration results from a T to C substitution at nucleotide position 13, causing the serine (S) at amino acid position 5 to be replaced by a proline (P). 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

Benign

0.069

BayesDel_addAF

Uncertain

0.14

BayesDel_noAF

Uncertain

-0.030

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.066

T;T

Eigen

Benign

0.16

Eigen_PC

Uncertain

0.35

FATHMM_MKL

Uncertain

0.88

LIST_S2

Benign

0.42

.;T

M_CAP

Benign

0.0024

MetaRNN

Benign

0.24

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.0

N;N

PrimateAI

Uncertain

0.74

PROVEAN

Benign

-0.96

N;N

REVEL

Benign

0.16

Sift

Uncertain

0.020

D;D

Sift4G

Benign

0.28

T;T

Polyphen

0.84

P;P

Vest4

0.53

MutPred

0.37

Loss of helix (P = 0.0033);Loss of helix (P = 0.0033);

MVP

0.50

MPC

0.64

ClinPred

0.42

GERP RS

6.2

Varity_R

0.32

gMVP

0.49

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