chr3-68733146-C-T

Variant names:

• chr3-68733146-C-T
• rs746528039
• NM_182522.5:c.419G>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_182522.5(TAFA4):​c.419G>A​(p.Arg140Gln) variant causes a missense change. The variant allele was found at a frequency of 0.000112 in 1,612,994 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R140L) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.000059 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00012 (1 hom.)
• Consequence: TAFA4 NM_182522.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.65
• Publications: 3 publications found

Genes affected

TAFA4 (HGNC:21591): (TAFA chemokine like family member 4) 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 have been observed for this gene. [provided by RefSeq, Nov 2011]

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.17699477).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_182522.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TAFA4	NM_182522.5	MANE Select	c.419G>A	p.Arg140Gln	missense	Exon 6 of 6	NP_872328.1	Q96LR4
	TAFA4	NM_001005527.3		c.419G>A	p.Arg140Gln	missense	Exon 6 of 6	NP_001005527.1	Q96LR4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TAFA4	ENST00000295569.12	TSL:1 MANE Select	c.419G>A	p.Arg140Gln	missense	Exon 6 of 6	ENSP00000295569.7	Q96LR4
	TAFA4	ENST00000917807.1		c.419G>A	p.Arg140Gln	missense	Exon 6 of 6	ENSP00000587866.1

Frequencies

GnomAD3 genomes AF: 0.0000592 AC: 9 AN: 152066 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000724

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000656

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000208

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000588

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000758 AC: 19 AN: 250678 AF XY: 0.0000885

Gnomad AFR exome AF: 0.0000616

Gnomad AMR exome AF: 0.0000579

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000544

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000972

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.000117 AC: 171 AN: 1460928 Hom.: 1 Cov.: 31 AF XY: 0.000116 AC XY: 84 AN XY: 726776

African (AFR) AF: 0.0000299 AC: 1 AN: 33430

American (AMR) AF: 0.0000895 AC: 4 AN: 44682

Ashkenazi Jewish (ASJ) AF: 0.0000766 AC: 2 AN: 26104

East Asian (EAS) AF: 0.000151 AC: 6 AN: 39690

South Asian (SAS) AF: 0.000244 AC: 21 AN: 86176

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53348

Middle Eastern (MID) AF: 0.00243 AC: 14 AN: 5754

European-Non Finnish (NFE) AF: 0.000105 AC: 117 AN: 1111394

Other (OTH) AF: 0.0000994 AC: 6 AN: 60350

GnomAD4 genome AF: 0.0000592 AC: 9 AN: 152066 Hom.: 0 Cov.: 32 AF XY: 0.0000673 AC XY: 5 AN XY: 74270

African (AFR) AF: 0.0000724 AC: 3 AN: 41426

American (AMR) AF: 0.0000656 AC: 1 AN: 15246

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5182

South Asian (SAS) AF: 0.000208 AC: 1 AN: 4814

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10604

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000588 AC: 4 AN: 68004

Other (OTH) AF: 0.00 AC: 0 AN: 2092

Alfa AF: 0.0000676 Hom.: 0

Bravo AF: 0.0000567

TwinsUK AF: 0.00 AC: 0

ALSPAC AF: 0.000519 AC: 2

ExAC AF: 0.0000577 AC: 7

EpiCase AF: 0.000109

EpiControl AF: 0.000357

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.38
BayesDel_addAF	Benign	-0.19	T
BayesDel_noAF	Benign	-0.31
CADD	Benign	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.015	T
Eigen	Benign	0.11
Eigen_PC	Benign	0.19
FATHMM_MKL	Uncertain	0.87	D
LIST_S2	Uncertain	0.91	D
M_CAP	Benign	0.0052	T
MetaRNN	Benign	0.18	T
MetaSVM	Benign	-0.97	T
MutationAssessor	Benign	0.46	N
PhyloP100		3.6
PrimateAI	Uncertain	0.56	T
PROVEAN	Benign	-1.1	N
REVEL	Benign	0.096
Sift	Benign	0.18	T
Sift4G	Benign	0.084	T
Polyphen		0.90	P
Vest4		0.47
MVP		0.10
MPC		0.33
ClinPred		0.076	T
GERP RS		4.1
Varity_R		0.092
gMVP		0.12
Mutation Taster		=91/9	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs746528039; hg19: chr3-68782297; COSMIC: COSV55134313;