NM_006700.3:c.29C>A

Variant names:

• chr12-112130551-C-A
• NM_006700.3:c.29C>A

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_006700.3(TRAFD1):​c.29C>A​(p.Thr10Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: TRAFD1 NM_006700.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.03
• Publications: 0 publications found

Genes affected

TRAFD1 (HGNC:24808): (TRAF-type zinc finger domain containing 1) The innate immune system confers host defense against viral and microbial infection, and TRAFD1 is a negative feedback regulator that controls excessive immune responses (Sanada et al., 2008 [PubMed 18849341]).[supplied by OMIM, Dec 2009]

ACMG classification

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

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.25075805).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006700.3. 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
	TRAFD1	NM_006700.3	MANE Select	c.29C>A	p.Thr10Asn	missense	Exon 2 of 12	NP_006691.1	O14545-1
	TRAFD1	NM_001143906.2		c.29C>A	p.Thr10Asn	missense	Exon 2 of 12	NP_001137378.1	O14545-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TRAFD1	ENST00000412615.7	TSL:1 MANE Select	c.29C>A	p.Thr10Asn	missense	Exon 2 of 12	ENSP00000396526.2	O14545-1
	TRAFD1	ENST00000550051.5	TSL:1	n.122C>A		non_coding_transcript_exon	Exon 2 of 5
	TRAFD1	ENST00000880370.1		c.29C>A	p.Thr10Asn	missense	Exon 2 of 12	ENSP00000550429.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 29

GnomAD4 genome Cov.: 32

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	Benign	0.15
BayesDel_addAF	Benign	-0.20	T
BayesDel_noAF	Benign	-0.53
CADD	Benign	21
DANN	Benign	0.97
DEOGEN2	Uncertain	0.58	D
Eigen	Benign	0.12
Eigen_PC	Benign	0.049
FATHMM_MKL	Uncertain	0.77	D
LIST_S2	Benign	0.71	T
M_CAP	Benign	0.0073	T
MetaRNN	Benign	0.25	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.8	L
PhyloP100		2.0
PrimateAI	Benign	0.44	T
PROVEAN	Uncertain	-2.6	D
REVEL	Benign	0.14
Sift	Uncertain	0.021	D
Sift4G	Uncertain	0.0080	D
Polyphen		0.99	D
Vest4		0.37
MutPred		0.40		Gain of helix (P = 0.0325)
MVP		0.31
MPC		0.37
ClinPred		0.74	D
GERP RS		4.2
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.080
gMVP		0.45
Mutation Taster		=85/15	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

hg19: chr12-112568355;