chr6-42232836-G-C

Position:

• chr6-42232836-G-C

Variant summary

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

The NM_001395490.1(TRERF1):​c.3159C>G​(p.Asn1053Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000685 in 1,459,790 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: TRERF1 NM_001395490.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.40

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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TRERF1	NM_001395490.1	c.3159C>G	p.Asn1053Lys	missense_variant	17/18	ENST00000695948.1
LOC105375061	XR_001744122.2	n.122-1524G>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TRERF1	ENST00000695948.1	c.3159C>G	p.Asn1053Lys	missense_variant	17/18		NM_001395490.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.85e-7 AC: 1 AN: 1459790 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 725942

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 9.00e-7

Gnomad4 OTH exome AF: 0.00

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

Jan 03, 2024

The c.3123C>G (p.N1041K) alteration is located in exon 17 (coding exon 13) of the TRERF1 gene. This alteration results from a C to G substitution at nucleotide position 3123, causing the asparagine (N) at amino acid position 1041 to be replaced by a lysine (K). 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	Pathogenic	0.79
BayesDel_addAF	Benign	-0.17	T
BayesDel_noAF	Benign	-0.49
CADD	Benign	23
DANN	Uncertain	0.99
DEOGEN2	Benign	0.022	T;T;.;.;.
Eigen	Uncertain	0.22
Eigen_PC	Uncertain	0.28
FATHMM_MKL	Uncertain	0.90	D
LIST_S2	Uncertain	0.90	D;D;D;D;D
M_CAP	Benign	0.0072	T
MetaRNN	Uncertain	0.46	T;T;T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.97	.;L;.;.;.
MutationTaster	Benign	0.99	D;D;D;N;N
PrimateAI	Uncertain	0.79	T
PROVEAN	Benign	-1.9	N;N;.;N;N
REVEL	Benign	0.056
Sift	Benign	0.047	D;D;.;D;D
Sift4G	Benign	0.067	T;T;D;D;D
Polyphen		0.92	P;P;P;.;P
Vest4		0.61
MutPred		0.30		Gain of methylation at N1061 (P = 0.0071);.;.;.;.;
MVP		0.48
MPC		0.74
ClinPred		0.61	D
GERP RS		4.7
Varity_R		0.11
gMVP		0.25

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: chr6-42200574;