chr6-42236314-G-A

Position:

• chr6-42236314-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001395490.1(TRERF1):​c.2957C>T​(p.Ser986Phe) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: TRERF1 NM_001395490.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.19

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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.34874842).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TRERF1	NM_001395490.1	c.2957C>T	p.Ser986Phe	missense_variant	16/18	ENST00000695948.1	NP_001382419.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TRERF1	ENST00000695948.1	c.2957C>T	p.Ser986Phe	missense_variant	16/18		NM_001395490.1	ENSP00000512293.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

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 23, 2024

The c.2957C>T (p.S986F) alteration is located in exon 16 (coding exon 12) of the TRERF1 gene. This alteration results from a C to T substitution at nucleotide position 2957, causing the serine (S) at amino acid position 986 to be replaced by a phenylalanine (F). 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	0.16
BayesDel_addAF	Benign	-0.096	T
BayesDel_noAF	Benign	-0.38
CADD	Pathogenic	28
DANN	Uncertain	1.0
DEOGEN2	Benign	0.069	T;T;.;.;.
Eigen	Uncertain	0.51
Eigen_PC	Uncertain	0.57
FATHMM_MKL	Uncertain	0.89	D
LIST_S2	Uncertain	0.88	D;D;D;D;D
M_CAP	Benign	0.0096	T
MetaRNN	Benign	0.35	T;T;T;T;T
MetaSVM	Benign	-1.2	T
MutationAssessor	Benign	1.7	.;L;.;.;.
PrimateAI	Uncertain	0.50	T
PROVEAN	Uncertain	-3.4	D;D;.;D;D
REVEL	Benign	0.090
Sift	Uncertain	0.0020	D;D;.;D;D
Sift4G	Uncertain	0.0090	D;D;D;D;D
Polyphen		0.77	P;P;P;.;P
Vest4		0.52
MutPred		0.21		Loss of phosphorylation at S1006 (P = 0.0017);.;.;.;.;
MVP		0.13
MPC		1.2
ClinPred		0.96	D
GERP RS		5.6
Varity_R		0.20
gMVP		0.32

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: chr6-42204052; COSMIC: COSV61677345;