12-112130551-C-A

Variant names:

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

Variant summary

Our verdict is Uncertain significance. Variant got 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. 14/21 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

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

Verdict is Uncertain_significance. Variant got 0 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TRAFD1	NM_006700.3	c.29C>A	p.Thr10Asn	missense_variant	Exon 2 of 12	ENST00000412615.7	NP_006691.1
TRAFD1	NM_001143906.2	c.29C>A	p.Thr10Asn	missense_variant	Exon 2 of 12		NP_001137378.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TRAFD1	ENST00000412615.7	c.29C>A	p.Thr10Asn	missense_variant	Exon 2 of 12	1	NM_006700.3	ENSP00000396526.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 29

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Mar 24, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.29C>A (p.T10N) alteration is located in exon 2 (coding exon 1) of the TRAFD1 gene. This alteration results from a C to A substitution at nucleotide position 29, causing the threonine (T) at amino acid position 10 to be replaced by an asparagine (N). 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	0.15
BayesDel_addAF	Benign	-0.20	T
BayesDel_noAF	Benign	-0.53
CADD	Benign	21
DANN	Benign	0.97
DEOGEN2	Uncertain	0.58	D;T;D;T
Eigen	Benign	0.12
Eigen_PC	Benign	0.049
FATHMM_MKL	Uncertain	0.77	D
LIST_S2	Benign	0.71	.;T;T;T
M_CAP	Benign	0.0073	T
MetaRNN	Benign	0.25	T;T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.8	L;.;L;.
PrimateAI	Benign	0.44	T
PROVEAN	Uncertain	-2.6	D;D;D;D
REVEL	Benign	0.14
Sift	Uncertain	0.021	D;T;D;D
Sift4G	Uncertain	0.0080	D;T;D;D
Polyphen		0.99	D;.;D;D
Vest4		0.37
MutPred		0.40		Gain of helix (P = 0.0325);Gain of helix (P = 0.0325);Gain of helix (P = 0.0325);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

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr12-112568355;