chr22-48646720-C-T

Variant names:

• chr22-48646720-C-T
• rs767438176
• NM_001082967.3:c.236C>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

The NM_001082967.3(TAFA5):​c.236C>T​(p.Thr79Met) variant causes a missense change. The variant allele was found at a frequency of 0.000051 in 1,589,314 control chromosomes in the GnomAD database, including 1 homozygotes. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000059 (0 hom., cov: 33)
  • Exomes 𝑓: 0.000050 (1 hom.)
• Consequence: TAFA5 NM_001082967.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.18
• Publications: 1 publications found

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

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001082967.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TAFA5	NM_001082967.3	MANE Select	c.236C>T	p.Thr79Met	missense	Exon 2 of 4	NP_001076436.1	Q7Z5A7-1
	TAFA5	NM_015381.7		c.215C>T	p.Thr72Met	missense	Exon 2 of 4	NP_056196.2	Q7Z5A7-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TAFA5	ENST00000402357.6	TSL:1 MANE Select	c.236C>T	p.Thr79Met	missense	Exon 2 of 4	ENSP00000383933.2	Q7Z5A7-1
	TAFA5	ENST00000336769.9	TSL:4	c.236C>T	p.Thr79Met	missense	Exon 2 of 4	ENSP00000336812.5	B1B1J6
	TAFA5	ENST00000358295.9	TSL:2	c.215C>T	p.Thr72Met	missense	Exon 2 of 4	ENSP00000351043.5	Q7Z5A7-2

Frequencies

GnomAD3 genomes AF: 0.0000592 AC: 9 AN: 152144 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000131

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000882

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000632 AC: 13 AN: 205714 AF XY: 0.0000790

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000130

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000554

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000501 AC: 72 AN: 1437170 Hom.: 1 Cov.: 31 AF XY: 0.0000644 AC XY: 46 AN XY: 714164

African (AFR) AF: 0.0000301 AC: 1 AN: 33214

American (AMR) AF: 0.000119 AC: 5 AN: 42090

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25766

East Asian (EAS) AF: 0.0000257 AC: 1 AN: 38926

South Asian (SAS) AF: 0.000189 AC: 16 AN: 84524

European-Finnish (FIN) AF: 0.0000225 AC: 1 AN: 44388

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5700

European-Non Finnish (NFE) AF: 0.0000399 AC: 44 AN: 1102978

Other (OTH) AF: 0.0000671 AC: 4 AN: 59584

GnomAD4 genome AF: 0.0000592 AC: 9 AN: 152144 Hom.: 0 Cov.: 33 AF XY: 0.0000673 AC XY: 5 AN XY: 74310

African (AFR) AF: 0.00 AC: 0 AN: 41424

American (AMR) AF: 0.000131 AC: 2 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5180

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4828

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10628

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000882 AC: 6 AN: 68006

Other (OTH) AF: 0.00 AC: 0 AN: 2094

Alfa AF: 0.0000453 Hom.: 0

Bravo AF: 0.0000718

ExAC AF: 0.0000422 AC: 5

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.47
BayesDel_addAF	Pathogenic	0.26	D
BayesDel_noAF	Pathogenic	0.38
CADD	Pathogenic	30
DANN	Uncertain	1.0
DEOGEN2	Benign	0.37	T
Eigen	Pathogenic	0.78
Eigen_PC	Pathogenic	0.74
FATHMM_MKL	Uncertain	0.92	D
LIST_S2	Uncertain	0.95	D
M_CAP	Uncertain	0.28	D
MetaRNN	Uncertain	0.69	D
MetaSVM	Uncertain	-0.026	T
MutationAssessor	Uncertain	2.4	M
PhyloP100		5.2
PrimateAI	Pathogenic	0.88	D
PROVEAN	Pathogenic	-5.9	D
REVEL	Uncertain	0.44
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0	D
Polyphen		1.0	D
Vest4		0.78
MutPred		0.52		Loss of phosphorylation at T79 (P = 0.0398)
MVP		0.17
MPC		1.7
ClinPred		0.65	D
GERP RS		5.2
Varity_R		0.58
gMVP		0.79
Mutation Taster		=97/3	polymorphism

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: rs767438176; hg19: chr22-49042532; COSMIC: COSV100385322;