rs181558760

Variant names:

• chr12-61867337-C-A
• rs181558760
• NM_178539.5:c.89G>T

Your query was ambiguous. Multiple possible variants found:

• chr12-61867337-C-A
• chr12-61867337-C-T

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_178539.5(TAFA2):​c.89G>T​(p.Ser30Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000169 in 1,597,766 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000033 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000015 (0 hom.)
• Consequence: TAFA2 NM_178539.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.01
• Publications: 0 publications found

Genes affected

TAFA2 (HGNC:21589): (TAFA chemokine like family member 2) 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

Our verdict: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.062352955).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TAFA2	NM_178539.5	c.89G>T	p.Ser30Ile	missense_variant	Exon 2 of 5	ENST00000416284.8	NP_848634.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TAFA2	ENST00000416284.8	c.89G>T	p.Ser30Ile	missense_variant	Exon 2 of 5	1	NM_178539.5	ENSP00000393987.3

Frequencies

GnomAD3 genomes AF: 0.0000331 AC: 5 AN: 151080 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000330

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: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000821 AC: 20 AN: 243578 AF XY: 0.0000911

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000603

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000152 AC: 22 AN: 1446600 Hom.: 0 Cov.: 29 AF XY: 0.0000194 AC XY: 14 AN XY: 719968

African (AFR) AF: 0.00 AC: 0 AN: 32578

American (AMR) AF: 0.000512 AC: 22 AN: 42964

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25904

East Asian (EAS) AF: 0.00 AC: 0 AN: 39408

South Asian (SAS) AF: 0.00 AC: 0 AN: 84066

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52984

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5730

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1103230

Other (OTH) AF: 0.00 AC: 0 AN: 59736

GnomAD4 genome AF: 0.0000331 AC: 5 AN: 151166 Hom.: 0 Cov.: 32 AF XY: 0.0000136 AC XY: 1 AN XY: 73790

African (AFR) AF: 0.00 AC: 0 AN: 41242

American (AMR) AF: 0.000330 AC: 5 AN: 15166

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3466

East Asian (EAS) AF: 0.00 AC: 0 AN: 5146

South Asian (SAS) AF: 0.00 AC: 0 AN: 4778

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10216

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 292

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 67848

Other (OTH) AF: 0.00 AC: 0 AN: 2100

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000416

ExAC AF: 0.0000412 AC: 5

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Jul 18, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.89G>T (p.S30I) alteration is located in exon 2 (coding exon 1) of the FAM19A2 gene. This alteration results from a G to T substitution at nucleotide position 89, causing the serine (S) at amino acid position 30 to be replaced by an isoleucine (I). 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	0.11
BayesDel_addAF	Benign	-0.30	T
BayesDel_noAF	Benign	-0.31
CADD	Uncertain	25
DANN	Uncertain	0.99
DEOGEN2	Benign	0.024	T;T;.;T;.;.
Eigen	Benign	-0.15
Eigen_PC	Benign	0.093
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Benign	0.84	.;T;T;T;T;T
M_CAP	Benign	0.0037	T
MetaRNN	Benign	0.062	T;T;T;T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.34	N;N;.;.;.;.
PhyloP100		3.0
PrimateAI	Uncertain	0.60	T
PROVEAN	Benign	-2.3	N;N;D;N;N;N
REVEL	Benign	0.092
Sift	Uncertain	0.029	D;D;D;D;D;D
Sift4G	Uncertain	0.036	D;D;D;.;T;.
Polyphen		0.012	B;B;.;.;.;.
Vest4		0.46
MVP		0.12
MPC		0.70
ClinPred		0.16	T
GERP RS		4.8
Varity_R		0.33
gMVP		0.49
Mutation Taster		=40/60	disease causing

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: rs181558760; hg19: chr12-62261118;