3-68417403-G-T

Position:

• chr3-68417403-G-T

Variant summary

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

The NM_213609.4(TAFA1):​c.242G>T​(p.Arg81Leu) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: TAFA1 NM_213609.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.67

Genes affected

TAFA1 (HGNC:21587): (TAFA chemokine like family member 1) 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, Jul 2008]

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/exons	MANE	Protein	UniProt
TAFA1	NM_213609.4	c.242G>T	p.Arg81Leu	missense_variant	3/5	ENST00000478136.6	NP_998774.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TAFA1	ENST00000478136.6	c.242G>T	p.Arg81Leu	missense_variant	3/5	1	NM_213609.4	ENSP00000418575	P1
TAFA1	ENST00000496687.1	c.242G>T	p.Arg81Leu	missense_variant	2/4	1		ENSP00000417496	P1
TAFA1	ENST00000491017.1	n.630G>T		non_coding_transcript_exon_variant	5/5	5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

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

Feb 09, 2023

The c.242G>T (p.R81L) alteration is located in exon 3 (coding exon 2) of the FAM19A1 gene. This alteration results from a G to T substitution at nucleotide position 242, causing the arginine (R) at amino acid position 81 to be replaced by a leucine (L). 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	0.48
BayesDel_addAF	Uncertain	0.078	D
BayesDel_noAF	Benign	-0.13
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Benign	0.21	T;T;.
Eigen	Uncertain	0.21
Eigen_PC	Uncertain	0.23
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Uncertain	0.91	.;D;D
M_CAP	Benign	0.011	T
MetaRNN	Uncertain	0.51	D;D;D
MetaSVM	Benign	-0.94	T
MutationAssessor	Benign	0.81	L;L;.
MutationTaster	Benign	0.74	N;N
PrimateAI	Pathogenic	0.88	D
PROVEAN	Uncertain	-2.9	D;D;.
REVEL	Benign	0.24
Sift	Benign	0.065	T;T;.
Sift4G	Benign	0.11	T;T;T
Polyphen		0.90	P;P;.
Vest4		0.76
MutPred		0.31		Loss of disorder (P = 0.0572);Loss of disorder (P = 0.0572);.;
MVP		0.13
MPC		0.99
ClinPred		0.98	D
GERP RS		4.7
Varity_R		0.25
gMVP		0.44

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: chr3-68466553;