1-112722295-C-A

Position:

• chr1-112722295-C-A

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_182759.3(TAFA3):​c.62C>A​(p.Ala21Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: TAFA3 NM_182759.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.159

Genes affected

TAFA3 (HGNC:21590): (TAFA chemokine like family member 3) 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 encoding multiple isoforms have been observed for this gene. [provided by RefSeq, Nov 2011]

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.41710627).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TAFA3	NM_182759.3	c.62C>A	p.Ala21Asp	missense_variant	3/6	ENST00000361886.4
TAFA3	NM_001004440.2	c.62C>A	p.Ala21Asp	missense_variant	3/6
TAFA3	NR_169586.1	n.516C>A		non_coding_transcript_exon_variant	3/6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TAFA3	ENST00000361886.4	c.62C>A	p.Ala21Asp	missense_variant	3/6	1	NM_182759.3	P1
TAFA3	ENST00000369630.7	c.62C>A	p.Ala21Asp	missense_variant	2/5	1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Aug 10, 2021

The c.62C>A (p.A21D) alteration is located in exon 2 (coding exon 1) of the FAM19A3 gene. This alteration results from a C to A substitution at nucleotide position 62, causing the alanine (A) at amino acid position 21 to be replaced by an aspartic acid (D). 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	Uncertain	0.37
BayesDel_addAF	Uncertain	0.14	D
BayesDel_noAF	Uncertain	-0.040
CADD	Benign	14
DANN	Uncertain	0.97
DEOGEN2	Benign	0.020	.;T
Eigen	Benign	-0.44
Eigen_PC	Benign	-0.49
FATHMM_MKL	Benign	0.47	N
LIST_S2	Benign	0.59	T;T
M_CAP	Benign	0.012	T
MetaRNN	Benign	0.42	T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.0	M;M
MutationTaster	Benign	1.0	N;N
PrimateAI	Benign	0.32	T
PROVEAN	Uncertain	-2.6	D;N
REVEL	Benign	0.19
Sift	Uncertain	0.0040	D;D
Sift4G	Uncertain	0.015	D;T
Polyphen		0.97	D;B
Vest4		0.75
MutPred		0.46		Loss of MoRF binding (P = 0.0592);Loss of MoRF binding (P = 0.0592);
MVP		0.040
MPC		1.3
ClinPred		0.91	D
GERP RS		0.31
Varity_R		0.17
gMVP		0.82

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: chr1-113264917;