3-68752952-C-A

Variant names:

• chr3-68752952-C-A
• rs368834384
• NM_182522.5:c.197G>T

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_182522.5(TAFA4):​c.197G>T​(p.Arg66Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000821 in 1,461,856 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts 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. R66H) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000082 (0 hom.)
• Consequence: TAFA4 NM_182522.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.68
• 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: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.33237463).

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.197G>T	p.Arg66Leu	missense	Exon 4 of 6	NP_872328.1	Q96LR4
	TAFA4	NM_001005527.3		c.197G>T	p.Arg66Leu	missense	Exon 4 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.197G>T	p.Arg66Leu	missense	Exon 4 of 6	ENSP00000295569.7	Q96LR4
	TAFA4	ENST00000917807.1		c.197G>T	p.Arg66Leu	missense	Exon 4 of 6	ENSP00000587866.1
	TAFA4	ENST00000495737.1	TSL:4	c.197G>T	p.Arg66Leu	missense	Exon 4 of 4	ENSP00000419439.1	C9JUW7

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.0000239 AC: 6 AN: 251156 AF XY: 0.0000147

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000578

Gnomad ASJ exome AF: 0.0000993

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000176

Gnomad OTH exome AF: 0.000163

GnomAD4 exome AF: 0.00000821 AC: 12 AN: 1461856 Hom.: 0 Cov.: 31 AF XY: 0.00000963 AC XY: 7 AN XY: 727230

African (AFR) AF: 0.0000299 AC: 1 AN: 33480

American (AMR) AF: 0.0000894 AC: 4 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.000230 AC: 6 AN: 26134

East Asian (EAS) AF: 0.00 AC: 0 AN: 39698

South Asian (SAS) AF: 0.00 AC: 0 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53410

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 8.99e-7 AC: 1 AN: 1111990

Other (OTH) AF: 0.00 AC: 0 AN: 60394

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000756

ExAC AF: 0.00000824 AC: 1

EpiCase AF: 0.0000545

EpiControl AF: 0.00

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	Pathogenic	0.61
BayesDel_addAF	Benign	0.0024	T
BayesDel_noAF	Benign	-0.15
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.22	T
Eigen	Uncertain	0.40
Eigen_PC	Uncertain	0.41
FATHMM_MKL	Uncertain	0.91	D
LIST_S2	Uncertain	0.96	D
M_CAP	Benign	0.021	T
MetaRNN	Benign	0.33	T
MetaSVM	Benign	-0.71	T
MutationAssessor	Uncertain	2.1	M
PhyloP100		2.7
PrimateAI	Uncertain	0.60	T
PROVEAN	Pathogenic	-5.6	D
REVEL	Benign	0.18
Sift	Uncertain	0.0020	D
Sift4G	Uncertain	0.0050	D
Polyphen		0.73	P
Vest4		0.73
MutPred		0.32		Loss of disorder (P = 0.0189)
MVP		0.040
MPC		0.63
ClinPred		0.98	D
GERP RS		4.6
Varity_R		0.58
gMVP		0.60
Mutation Taster		=69/31	polymorphism

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

Other links and lift over

dbSNP: rs368834384; hg19: chr3-68802103;