NM_001082967.3:c.180G>A

Variant names:

• chr22-48646664-G-A
• rs35316568
• NM_001082967.3:c.180G>A

Variant summary

Our verdict is Benign. The variant received -19 ACMG points: 0P and 19B. BP4_Moderate BP6_Very_Strong BP7 BS1 BS2

The NM_001082967.3(TAFA5):​c.180G>A​(p.Thr60Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00631 in 1,612,032 control chromosomes in the GnomAD database, including 106 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0053 (13 hom., cov: 33)
  • Exomes 𝑓: 0.0064 (93 hom.)
• Consequence: TAFA5 NM_001082967.3 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.549
• 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: Benign. The variant received -19 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.36).
• BP6: Variant 22-48646664-G-A is Benign according to our data. Variant chr22-48646664-G-A is described in ClinVar as Benign. ClinVar VariationId is 778959.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=0.549 with no splicing effect.
• BS1: Variant frequency is greater than expected in population sas. GnomAd4 allele frequency = 0.00525 (800/152306) while in subpopulation SAS AF = 0.0228 (110/4828). AF 95% confidence interval is 0.0193. There are 13 homozygotes in GnomAd4. There are 421 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 13 gene

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.180G>A	p.Thr60Thr	synonymous	Exon 2 of 4	NP_001076436.1	Q7Z5A7-1
	TAFA5	NM_015381.7		c.159G>A	p.Thr53Thr	synonymous	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.180G>A	p.Thr60Thr	synonymous	Exon 2 of 4	ENSP00000383933.2	Q7Z5A7-1
	TAFA5	ENST00000336769.9	TSL:4	c.180G>A	p.Thr60Thr	synonymous	Exon 2 of 4	ENSP00000336812.5	B1B1J6
	TAFA5	ENST00000358295.9	TSL:2	c.159G>A	p.Thr53Thr	synonymous	Exon 2 of 4	ENSP00000351043.5	Q7Z5A7-2

Frequencies

GnomAD3 genomes AF: 0.00528 AC: 804 AN: 152188 Hom.: 14 Cov.: 33

Gnomad AFR AF: 0.00130

Gnomad AMI AF: 0.0307

Gnomad AMR AF: 0.00687

Gnomad ASJ AF: 0.0242

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.0228

Gnomad FIN AF: 0.00169

Gnomad MID AF: 0.0475

Gnomad NFE AF: 0.00538

Gnomad OTH AF: 0.0110

GnomAD2 exomes AF: 0.00767 AC: 1883 AN: 245520 AF XY: 0.00880

Gnomad AFR exome AF: 0.000526

Gnomad AMR exome AF: 0.00299

Gnomad ASJ exome AF: 0.0236

Gnomad EAS exome AF: 0.0000559

Gnomad FIN exome AF: 0.000957

Gnomad NFE exome AF: 0.00653

Gnomad OTH exome AF: 0.0124

GnomAD4 exome AF: 0.00642 AC: 9378 AN: 1459726 Hom.: 93 Cov.: 31 AF XY: 0.00721 AC XY: 5234 AN XY: 726230

African (AFR) AF: 0.00122 AC: 41 AN: 33472

American (AMR) AF: 0.00356 AC: 159 AN: 44692

Ashkenazi Jewish (ASJ) AF: 0.0257 AC: 671 AN: 26104

East Asian (EAS) AF: 0.000126 AC: 5 AN: 39690

South Asian (SAS) AF: 0.0254 AC: 2188 AN: 86236

European-Finnish (FIN) AF: 0.000774 AC: 40 AN: 51706

Middle Eastern (MID) AF: 0.0473 AC: 273 AN: 5768

European-Non Finnish (NFE) AF: 0.00493 AC: 5480 AN: 1111724

Other (OTH) AF: 0.00864 AC: 521 AN: 60334

GnomAD4 genome AF: 0.00525 AC: 800 AN: 152306 Hom.: 13 Cov.: 33 AF XY: 0.00565 AC XY: 421 AN XY: 74470

African (AFR) AF: 0.00130 AC: 54 AN: 41568

American (AMR) AF: 0.00686 AC: 105 AN: 15308

Ashkenazi Jewish (ASJ) AF: 0.0242 AC: 84 AN: 3472

East Asian (EAS) AF: 0.000194 AC: 1 AN: 5162

South Asian (SAS) AF: 0.0228 AC: 110 AN: 4828

European-Finnish (FIN) AF: 0.00169 AC: 18 AN: 10622

Middle Eastern (MID) AF: 0.0442 AC: 13 AN: 294

European-Non Finnish (NFE) AF: 0.00538 AC: 366 AN: 68028

Other (OTH) AF: 0.00994 AC: 21 AN: 2112

Alfa AF: 0.00681 Hom.: 2

Bravo AF: 0.00500

Asia WGS AF: 0.0100 AC: 35 AN: 3478

EpiCase AF: 0.00851

EpiControl AF: 0.00931

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.36
CADD	Benign	5.1
DANN	Benign	0.88
PhyloP100		0.55
Mutation Taster		=100/0	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: rs35316568; hg19: chr22-49042476; COSMIC: COSV60987143;