chr3-68880741-C-T

Variant names:

• chr3-68880741-C-T
• rs751781952
• NM_182522.5:c.119G>A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_182522.5(TAFA4):​c.119G>A​(p.Arg40Gln) variant causes a missense change. The variant allele was found at a frequency of 0.0000366 in 1,613,814 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 (★).

• Frequency:
  • Genomes: 𝑓 0.000066 (0 hom., cov: 33)
  • Exomes 𝑓: 0.000034 (0 hom.)
• Consequence: TAFA4 NM_182522.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.75

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

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=0.13809747).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TAFA4	NM_182522.5	c.119G>A	p.Arg40Gln	missense_variant	Exon 3 of 6	ENST00000295569.12	NP_872328.1
TAFA4	NM_001005527.3	c.119G>A	p.Arg40Gln	missense_variant	Exon 3 of 6		NP_001005527.1
TAFA4	XM_011533371.2	c.119G>A	p.Arg40Gln	missense_variant	Exon 3 of 6		XP_011531673.1
TAFA4	XM_011533372.2	c.119G>A	p.Arg40Gln	missense_variant	Exon 3 of 6		XP_011531674.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TAFA4	ENST00000295569.12	c.119G>A	p.Arg40Gln	missense_variant	Exon 3 of 6	1	NM_182522.5	ENSP00000295569.7
TAFA4	ENST00000495737.1	c.119G>A	p.Arg40Gln	missense_variant	Exon 3 of 4	4		ENSP00000419439.1
TAFA4	ENST00000634242.1	c.119G>A	p.Arg40Gln	missense_variant	Exon 6 of 7	5		ENSP00000489092.1

Frequencies

GnomAD3 genomes AF: 0.0000657 AC: 10 AN: 152172 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.000193

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000654

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.00

GnomAD3 exomes AF: 0.0000359 AC: 9 AN: 250860 Hom.: 0 AF XY: 0.0000369 AC XY: 5 AN XY: 135536

Gnomad AFR exome AF: 0.000185

Gnomad AMR exome AF: 0.000116

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: 0.0000177

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000335 AC: 49 AN: 1461642 Hom.: 0 Cov.: 30 AF XY: 0.0000330 AC XY: 24 AN XY: 727108

Gnomad4 AFR exome AF: 0.000209

Gnomad4 AMR exome AF: 0.000112

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: 0.0000315

Gnomad4 OTH exome AF: 0.0000166

GnomAD4 genome AF: 0.0000657 AC: 10 AN: 152172 Hom.: 0 Cov.: 33 AF XY: 0.0000404 AC XY: 3 AN XY: 74330

Gnomad4 AFR AF: 0.000193

Gnomad4 AMR AF: 0.0000654

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000147

Gnomad4 OTH AF: 0.00

Bravo AF: 0.0000604

ExAC AF: 0.0000247 AC: 3

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Jan 04, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.119G>A (p.R40Q) alteration is located in exon 3 (coding exon 2) of the FAM19A4 gene. This alteration results from a G to A substitution at nucleotide position 119, causing the arginine (R) at amino acid position 40 to be replaced by a glutamine (Q). 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	0.082
BayesDel_addAF	Benign	-0.22	T
BayesDel_noAF	Benign	-0.32
CADD	Uncertain	25
DANN	Uncertain	0.99
DEOGEN2	Benign	0.016	T;.;.
Eigen	Benign	-0.14
Eigen_PC	Benign	0.071
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Benign	0.74	T;T;T
M_CAP	Benign	0.0035	T
MetaRNN	Benign	0.14	T;T;T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	0.69	N;.;.
PrimateAI	Uncertain	0.56	T
PROVEAN	Benign	-0.88	N;N;.
REVEL	Benign	0.081
Sift	Benign	0.55	T;T;.
Sift4G	Benign	0.73	T;.;.
Polyphen		0.024	B;.;.
Vest4		0.58
MutPred		0.20		Loss of methylation at R40 (P = 0.0134);Loss of methylation at R40 (P = 0.0134);Loss of methylation at R40 (P = 0.0134);
MVP		0.067
MPC		0.23
ClinPred		0.13	T
GERP RS		5.1
Varity_R		0.16
gMVP		0.31

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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

Other links and lift over

dbSNP: rs751781952; hg19: chr3-68929892;