Variant 22-48646664-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_ModerateBP6_ModerateBP7BS1BS2

The NM_001082967.3(TAFA5):c.180G>A(p.Thr60=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00631 in 1,612,032 control chromosomes in the GnomAD database, including 106 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0053 ( 13 hom., cov: 33)

Exomes 𝑓: 0.0064 ( 93 hom. )

Consequence

TAFA5
NM_001082967.3 synonymous

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.549

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -13 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.36).

BP6

Variant 22-48646664-G-A is Benign according to our data. Variant chr22-48646664-G-A is described in ClinVar as [Benign]. Clinvar id is 778959.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=0.549 with no splicing effect.

BS1

Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.00525 (800/152306) while in subpopulation SAS AF= 0.0228 (110/4828). AF 95% confidence interval is 0.0193. There are 13 homozygotes in gnomad4. There are 421 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 13 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TAFA5	NM_001082967.3 linkuse as main transcript	c.180G>A	p.Thr60=	synonymous_variant	2/4	ENST00000402357.6
TAFA5	NM_015381.7 linkuse as main transcript	c.159G>A	p.Thr53=	synonymous_variant	2/4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TAFA5	ENST00000402357.6 linkuse as main transcript	c.180G>A	p.Thr60=	synonymous_variant	2/4	1	NM_001082967.3	P4	Q7Z5A7-1
TAFA5	ENST00000336769.9 linkuse as main transcript	c.180G>A	p.Thr60=	synonymous_variant	2/4	4
TAFA5	ENST00000358295.9 linkuse as main transcript	c.159G>A	p.Thr53=	synonymous_variant	2/4	2		A1	Q7Z5A7-2
TAFA5	ENST00000473898.1 linkuse as main transcript	n.120-61053G>A		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes

AF:

0.00528

AC:

804

AN:

152188

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00130

Gnomad AMI

AF:

0.0307

Gnomad AMR

AF:

0.00687

Gnomad ASJ

AF:

0.0242

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.0228

Gnomad FIN

AF:

0.00169

Gnomad MID

AF:

0.0475

Gnomad NFE

AF:

0.00538

Gnomad OTH

AF:

0.0110

GnomAD3 exomes

AF:

0.00767

AC:

1883

AN:

245520

Hom.:

AF XY:

0.00880

AC XY:

1180

AN XY:

134032

show subpopulations

Gnomad AFR exome

AF:

0.000526

Gnomad AMR exome

AF:

0.00299

Gnomad ASJ exome

AF:

0.0236

Gnomad EAS exome

AF:

0.0000559

Gnomad SAS exome

AF:

0.0236

Gnomad FIN exome

AF:

0.000957

Gnomad NFE exome

AF:

0.00653

Gnomad OTH exome

AF:

0.0124

GnomAD4 exome

AF:

0.00642

AC:

9378

AN:

1459726

Hom.:

Cov.:

AF XY:

0.00721

AC XY:

5234

AN XY:

726230

show subpopulations

Gnomad4 AFR exome

AF:

0.00122

Gnomad4 AMR exome

AF:

0.00356

Gnomad4 ASJ exome

AF:

0.0257

Gnomad4 EAS exome

AF:

0.000126

Gnomad4 SAS exome

AF:

0.0254

Gnomad4 FIN exome

AF:

0.000774

Gnomad4 NFE exome

AF:

0.00493

Gnomad4 OTH exome

AF:

0.00864

GnomAD4 genome

AF:

0.00525

AC:

800

AN:

152306

Hom.:

Cov.:

AF XY:

0.00565

AC XY:

421

AN XY:

74470

show subpopulations

Gnomad4 AFR

AF:

0.00130

Gnomad4 AMR

AF:

0.00686

Gnomad4 ASJ

AF:

0.0242

Gnomad4 EAS

AF:

0.000194

Gnomad4 SAS

AF:

0.0228

Gnomad4 FIN

AF:

0.00169

Gnomad4 NFE

AF:

0.00538

Gnomad4 OTH

AF:

0.00994

Alfa

AF:

0.00600

Hom.:

Bravo

AF:

0.00500

Asia WGS

AF:

0.0100

AC:

AN:

3478

EpiCase

AF:

0.00851

EpiControl

AF:

0.00931

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Feb 27, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.36

CADD

Benign

5.1

DANN

Benign

0.88

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