12-112151941-C-G

Position:

• chr12-112151941-C-G

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_006700.3(TRAFD1):​c.1420C>G​(p.Pro474Ala) 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: -0.136

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 Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.055032104).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TRAFD1	NM_006700.3	c.1420C>G	p.Pro474Ala	missense_variant	10/12	ENST00000412615.7	NP_006691.1
TRAFD1	NM_001143906.2	c.1420C>G	p.Pro474Ala	missense_variant	10/12		NP_001137378.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TRAFD1	ENST00000412615.7	c.1420C>G	p.Pro474Ala	missense_variant	10/12	1	NM_006700.3	ENSP00000396526.2
TRAFD1	ENST00000257604.9	c.1420C>G	p.Pro474Ala	missense_variant	10/12	2		ENSP00000257604.5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Oct 16, 2023

The c.1420C>G (p.P474A) alteration is located in exon 10 (coding exon 9) of the TRAFD1 gene. This alteration results from a C to G substitution at nucleotide position 1420, causing the proline (P) at amino acid position 474 to be replaced by an alanine (A). 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	0.063
BayesDel_addAF	Benign	-0.23	T
BayesDel_noAF	Benign	-0.56
CADD	Benign	7.8
DANN	Benign	0.90
DEOGEN2	Benign	0.072	T;T
Eigen	Benign	-0.73
Eigen_PC	Benign	-0.83
FATHMM_MKL	Benign	0.16	N
LIST_S2	Benign	0.58	.;T
M_CAP	Benign	0.0045	T
MetaRNN	Benign	0.055	T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.3	M;M
PrimateAI	Benign	0.27	T
PROVEAN	Benign	-1.4	N;N
REVEL	Benign	0.077
Sift	Uncertain	0.028	D;D
Sift4G	Benign	0.28	T;T
Polyphen		0.59	P;P
Vest4		0.16
MutPred		0.081		Gain of catalytic residue at P474 (P = 0.0327);Gain of catalytic residue at P474 (P = 0.0327);
MVP		0.20
MPC		0.11
ClinPred		0.11	T
GERP RS		-1.2
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.8
Varity_R		0.020
gMVP		0.22

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: chr12-112589745;