6-42228404-T-G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001395490.1(TRERF1):c.3580A>C(p.Thr1194Pro) 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: TRERF1 NM_001395490.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.752

Genes affected

TRERF1 (HGNC:18273): (transcriptional regulating factor 1) This gene encodes a zinc-finger transcriptional regulating protein which interacts with CBP/p300 to regulate the human gene CYP11A1. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Jul 2014]

LOC105375061 (HGNC:):

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=0.10446578).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TRERF1	NM_001395490.1	c.3580A>C	p.Thr1194Pro	missense_variant	18/18	ENST00000695948.1
LOC105375061	XR_001744122.2	n.121+3545T>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TRERF1	ENST00000695948.1	c.3580A>C	p.Thr1194Pro	missense_variant	18/18		NM_001395490.1

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

Nov 29, 2023

The c.3544A>C (p.T1182P) alteration is located in exon 18 (coding exon 14) of the TRERF1 gene. This alteration results from a A to C substitution at nucleotide position 3544, causing the threonine (T) at amino acid position 1182 to be replaced by a proline (P). 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	0.086
BayesDel_addAF	Benign	-0.15	T
BayesDel_noAF	Benign	-0.45
Cadd	Benign	19
Dann	Uncertain	0.99
DEOGEN2	Benign	0.024	T;T;.;.;.
Eigen	Benign	-0.41
Eigen_PC	Benign	-0.31
FATHMM_MKL	Benign	0.74	D
LIST_S2	Benign	0.64	T;T;T;T;T
M_CAP	Benign	0.010	T
MetaRNN	Benign	0.10	T;T;T;T;T
MetaSVM	Benign	-1.0	T
MutationTaster	Benign	0.88	N;N;N;N;N
PrimateAI	Benign	0.33	T
PROVEAN	Benign	-1.6	N;N;.;N;N
REVEL	Benign	0.083
Sift	Benign	0.12	T;T;.;D;D
Sift4G	Benign	0.19	T;T;T;T;T
Polyphen		0.0	B;B;B;.;B
Vest4		0.23
MutPred		0.34		Loss of sheet (P = 0.0228);.;.;.;.;
MVP		0.31
MPC		1.4
ClinPred		0.29	T
GERP RS		0.51
Varity_R		0.27
gMVP		0.23

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: chr6-42196142;