NM_001395490.1:c.3002C>T

Variant names:

• chr6-42236269-G-A
• rs372620033
• NM_001395490.1:c.3002C>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_001395490.1(TRERF1):​c.3002C>T​(p.Pro1001Leu) variant causes a missense change. The variant allele was found at a frequency of 0.000118 in 1,612,828 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000066 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00012 (0 hom.)
• Consequence: TRERF1 NM_001395490.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.81
• Publications: 0 publications found

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]

TRERF1 Gene-Disease associations (from GenCC):

• complex neurodevelopmental disorder

  Inheritance: AR Classification: LIMITED Submitted by: Ambry Genetics

LOC105375061 (HGNC:):

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.093848914).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001395490.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TRERF1	NM_001395490.1	MANE Select	c.3002C>T	p.Pro1001Leu	missense	Exon 16 of 18	NP_001382419.1	A0A8Q3SI57
	TRERF1	NM_001297573.2		c.3062C>T	p.Pro1021Leu	missense	Exon 16 of 18	NP_001284502.1	Q05GC8
	TRERF1	NM_001391983.1		c.3002C>T	p.Pro1001Leu	missense	Exon 16 of 18	NP_001378912.1	Q96PN7-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TRERF1	ENST00000695948.1	MANE Select	c.3002C>T	p.Pro1001Leu	missense	Exon 16 of 18	ENSP00000512293.1	A0A8Q3SI57
	TRERF1	ENST00000541110.5	TSL:1	c.3062C>T	p.Pro1021Leu	missense	Exon 16 of 18	ENSP00000439689.1	Q05GC8
	TRERF1	ENST00000372922.8	TSL:1	c.3002C>T	p.Pro1001Leu	missense	Exon 16 of 18	ENSP00000362013.4	Q96PN7-1

Frequencies

GnomAD3 genomes AF: 0.0000657 AC: 10 AN: 152216 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000121

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000735

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000648 AC: 16 AN: 247086 AF XY: 0.0000674

Gnomad AFR exome AF: 0.0000629

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.000141

Gnomad NFE exome AF: 0.0000988

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.000123 AC: 180 AN: 1460612 Hom.: 0 Cov.: 32 AF XY: 0.000121 AC XY: 88 AN XY: 726512

African (AFR) AF: 0.000120 AC: 4 AN: 33458

American (AMR) AF: 0.00 AC: 0 AN: 44542

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26058

East Asian (EAS) AF: 0.00 AC: 0 AN: 39672

South Asian (SAS) AF: 0.0000116 AC: 1 AN: 85994

European-Finnish (FIN) AF: 0.000206 AC: 11 AN: 53276

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5762

European-Non Finnish (NFE) AF: 0.000142 AC: 158 AN: 1111508

Other (OTH) AF: 0.0000994 AC: 6 AN: 60342

GnomAD4 genome AF: 0.0000657 AC: 10 AN: 152216 Hom.: 0 Cov.: 32 AF XY: 0.0000538 AC XY: 4 AN XY: 74372

African (AFR) AF: 0.000121 AC: 5 AN: 41464

American (AMR) AF: 0.00 AC: 0 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5190

South Asian (SAS) AF: 0.00 AC: 0 AN: 4834

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10624

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000735 AC: 5 AN: 68028

Other (OTH) AF: 0.00 AC: 0 AN: 2090

Alfa AF: 0.000173 Hom.: 0

Bravo AF: 0.0000831

TwinsUK AF: 0.00 AC: 0

ALSPAC AF: 0.000259 AC: 1

ESP6500AA AF: 0.000227 AC: 1

ESP6500EA AF: 0.00 AC: 0

ExAC AF: 0.0000577 AC: 7

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.057
BayesDel_addAF	Benign	-0.35	T
BayesDel_noAF	Benign	-0.54
CADD	Benign	21
DANN	Uncertain	1.0
DEOGEN2	Benign	0.023	T
Eigen	Benign	-0.17
Eigen_PC	Benign	-0.036
FATHMM_MKL	Uncertain	0.88	D
LIST_S2	Benign	0.82	T
M_CAP	Benign	0.011	T
MetaRNN	Benign	0.094	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.6	L
PhyloP100		3.8
PrimateAI	Benign	0.40	T
PROVEAN	Benign	-1.6	N
REVEL	Benign	0.038
Sift	Benign	0.14	T
Sift4G	Benign	0.25	T
Polyphen		0.0080	B
Vest4		0.35
MVP		0.26
MPC		1.4
ClinPred		0.091	T
GERP RS		3.8
Varity_R		0.071
gMVP		0.28
Mutation Taster		=90/10	polymorphism

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

Other links and lift over

dbSNP: rs372620033; hg19: chr6-42204007; COSMIC: COSV61674024;