Variant chr1-112723024-C-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6_Moderate

The NM_182759.3(TAFA3):c.124C>A(p.Gln42Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00141 in 1,611,756 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00098 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0015 ( 1 hom. )

Consequence

TAFA3
NM_182759.3 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.93

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 Likely_benign. Variant got -4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.0057810545).

BP6

Variant 1-112723024-C-A is Benign according to our data. Variant chr1-112723024-C-A is described in ClinVar as [Likely_benign]. Clinvar id is 3173602.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
TAFA3	NM_182759.3 linkuse as main transcript	c.124C>A	p.Gln42Lys	missense_variant	4/6	ENST00000361886.4
TAFA3	NM_001004440.2 linkuse as main transcript	c.124C>A	p.Gln42Lys	missense_variant	4/6
TAFA3	NR_169586.1 linkuse as main transcript	n.578C>A		non_coding_transcript_exon_variant	4/6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TAFA3	ENST00000361886.4 linkuse as main transcript	c.124C>A	p.Gln42Lys	missense_variant	4/6	1	NM_182759.3	P1	Q7Z5A8-1
TAFA3	ENST00000369630.7 linkuse as main transcript	c.124C>A	p.Gln42Lys	missense_variant	3/5	1			Q7Z5A8-2

Frequencies

GnomAD3 genomes

AF:

0.000986

AC:

150

AN:

152180

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000169

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000720

Gnomad ASJ

AF:

0.00259

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00169

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.00150

Gnomad OTH

AF:

0.000957

GnomAD3 exomes

AF:

0.00112

AC:

276

AN:

246244

Hom.:

AF XY:

0.00110

AC XY:

147

AN XY:

133736

show subpopulations

Gnomad AFR exome

AF:

0.000251

Gnomad AMR exome

AF:

0.00102

Gnomad ASJ exome

AF:

0.00252

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000572

Gnomad NFE exome

AF:

0.00177

Gnomad OTH exome

AF:

0.000669

GnomAD4 exome

AF:

0.00145

AC:

2117

AN:

1459458

Hom.:

Cov.:

AF XY:

0.00141

AC XY:

1026

AN XY:

725972

show subpopulations

Gnomad4 AFR exome

AF:

0.000149

Gnomad4 AMR exome

AF:

0.00101

Gnomad4 ASJ exome

AF:

0.00261

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.000719

Gnomad4 NFE exome

AF:

0.00168

Gnomad4 OTH exome

AF:

0.00158

GnomAD4 genome

AF:

0.000985

AC:

150

AN:

152298

Hom.:

Cov.:

AF XY:

0.000980

AC XY:

AN XY:

74454

show subpopulations

Gnomad4 AFR

AF:

0.000168

Gnomad4 AMR

AF:

0.000719

Gnomad4 ASJ

AF:

0.00259

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00169

Gnomad4 NFE

AF:

0.00150

Gnomad4 OTH

AF:

0.000947

Alfa

AF:

0.00154

Hom.:

Bravo

AF:

0.000941

TwinsUK

AF:

0.00135

AC:

ALSPAC

AF:

0.00285

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.00233

AC:

ExAC

AF:

0.00124

AC:

150

EpiCase

AF:

0.00153

EpiControl

AF:

0.00166

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Feb 06, 2024

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.046

BayesDel_addAF

Benign

-0.65

BayesDel_noAF

Benign

-0.71

CADD

Benign

DANN

Benign

0.89

DEOGEN2

Benign

0.0026

.;T

Eigen

Benign

-0.90

Eigen_PC

Benign

-0.69

FATHMM_MKL

Benign

0.45

LIST_S2

Benign

0.72

T;T

M_CAP

Benign

0.0073

MetaRNN

Benign

0.0058

T;T

MetaSVM

Benign

-0.93

MutationAssessor

Benign

-1.9

N;N

MutationTaster

Benign

1.0

N;N

PrimateAI

Benign

0.34

PROVEAN

Benign

3.0

N;N

REVEL

Benign

0.10

Sift

Benign

1.0

T;T

Sift4G

Benign

1.0

T;T

Polyphen

0.0

B;B

Vest4

0.13

MVP

0.014

MPC

0.44

ClinPred

0.0096

GERP RS

0.71

Varity_R

0.056

gMVP

0.44

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