22-48707828-G-C

Variant names:

• chr22-48707828-G-C
• NM_001082967.3:c.374G>C

Variant summary

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

The NM_001082967.3(TAFA5):​c.374G>C​(p.Arg125Thr) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 34)
• Consequence: TAFA5 NM_001082967.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 8.56

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TAFA5	NM_001082967.3	c.374G>C	p.Arg125Thr	missense_variant	Exon 3 of 4	ENST00000402357.6	NP_001076436.1
TAFA5	NM_015381.7	c.353G>C	p.Arg118Thr	missense_variant	Exon 3 of 4		NP_056196.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TAFA5	ENST00000402357.6	c.374G>C	p.Arg125Thr	missense_variant	Exon 3 of 4	1	NM_001082967.3	ENSP00000383933.2

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 34

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Feb 28, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.374G>C (p.R125T) alteration is located in exon 3 (coding exon 3) of the FAM19A5 gene. This alteration results from a G to C substitution at nucleotide position 374, causing the arginine (R) at amino acid position 125 to be replaced by a threonine (T). 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	Pathogenic	0.95
BayesDel_addAF	Pathogenic	0.21	D
BayesDel_noAF	Uncertain	0.070
CADD	Pathogenic	29
DANN	Uncertain	0.98
DEOGEN2	Benign	0.15	T;.;.;.
Eigen	Uncertain	0.54
Eigen_PC	Uncertain	0.54
FATHMM_MKL	Uncertain	0.97	D
LIST_S2	Uncertain	0.92	D;D;D;D
M_CAP	Benign	0.064	D
MetaRNN	Uncertain	0.62	D;D;D;D
MetaSVM	Benign	-0.43	T
MutationAssessor	Uncertain	2.1	M;.;.;.
PrimateAI	Uncertain	0.73	T
PROVEAN	Uncertain	-4.0	D;D;D;D
REVEL	Uncertain	0.32
Sift	Uncertain	0.0020	D;D;D;D
Sift4G	Uncertain	0.0050	D;D;D;D
Polyphen		0.98	D;.;P;.
Vest4		0.71
MutPred		0.38		Loss of MoRF binding (P = 0.021);Loss of MoRF binding (P = 0.021);.;.;
MVP		0.14
MPC		2.0
ClinPred		0.98	D
GERP RS		4.5
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.45
gMVP		0.85

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr22-49103640;