rs761271480

Variant names:

• chr3-68752940-C-G
• rs761271480
• NM_182522.5:c.209G>C

Your query was ambiguous. Multiple possible variants found:

• chr3-68752940-C-G
• chr3-68752940-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP3

The NM_182522.5(TAFA4):​c.209G>C​(p.Arg70Pro) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R70Q) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: TAFA4 NM_182522.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.85

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 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.747

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TAFA4	NM_182522.5	c.209G>C	p.Arg70Pro	missense_variant	Exon 4 of 6	ENST00000295569.12	NP_872328.1
TAFA4	NM_001005527.3	c.209G>C	p.Arg70Pro	missense_variant	Exon 4 of 6		NP_001005527.1
TAFA4	XM_011533371.2	c.209G>C	p.Arg70Pro	missense_variant	Exon 4 of 6		XP_011531673.1
TAFA4	XM_011533372.2	c.209G>C	p.Arg70Pro	missense_variant	Exon 4 of 6		XP_011531674.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TAFA4	ENST00000295569.12	c.209G>C	p.Arg70Pro	missense_variant	Exon 4 of 6	1	NM_182522.5	ENSP00000295569.7
TAFA4	ENST00000495737.1	c.209G>C	p.Arg70Pro	missense_variant	Exon 4 of 4	4		ENSP00000419439.1
TAFA4	ENST00000634242.1	c.*36G>C		downstream_gene_variant		5		ENSP00000489092.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	1.0
BayesDel_addAF	Pathogenic	0.46	D
BayesDel_noAF	Pathogenic	0.42
CADD	Pathogenic	27
DANN	Uncertain	1.0
DEOGEN2	Benign	0.30	T;.
Eigen	Pathogenic	0.85
Eigen_PC	Pathogenic	0.83
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Pathogenic	0.99	D;D
M_CAP	Benign	0.050	D
MetaRNN	Pathogenic	0.75	D;D
MetaSVM	Uncertain	0.039	D
MutationAssessor	Uncertain	2.4	M;.
PrimateAI	Pathogenic	0.81	D
PROVEAN	Pathogenic	-6.9	D;D
REVEL	Pathogenic	0.69
Sift	Uncertain	0.0070	D;D
Sift4G	Uncertain	0.0090	D;.
Polyphen		1.0	D;.
Vest4		0.97
MutPred		0.37		Gain of relative solvent accessibility (P = 0.0166);Gain of relative solvent accessibility (P = 0.0166);
MVP		0.095
MPC		0.92
ClinPred		1.0	D
GERP RS		5.5
Varity_R		0.95
gMVP		0.86

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

LitVar

Other links and lift over

dbSNP: rs761271480; hg19: chr3-68802091;