19-58547430-A-T

Position:

• chr19-58547430-A-T

Variant summary

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

The NM_005762.3(TRIM28):​c.641A>T​(p.His214Leu) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: TRIM28 NM_005762.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.75

Genes affected

TRIM28 (HGNC:16384): (tripartite motif containing 28) The protein encoded by this gene mediates transcriptional control by interaction with the Kruppel-associated box repression domain found in many transcription factors. The protein localizes to the nucleus and is thought to associate with specific chromatin regions. The protein is a member of the tripartite motif family. This tripartite motif includes three zinc-binding domains, a RING, a B-box type 1 and a B-box type 2, and a coiled-coil region. [provided by RefSeq, Jul 2008]

TRIM28 (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	Protein	UniProt
TRIM28	NM_005762.3	c.641A>T	p.His214Leu	missense_variant	4/17	ENST00000253024.10	NP_005753.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TRIM28	ENST00000253024.10	c.641A>T	p.His214Leu	missense_variant	4/17	1	NM_005762.3	ENSP00000253024.4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 35

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

Mar 25, 2024

The c.641A>T (p.H214L) alteration is located in exon 4 (coding exon 4) of the TRIM28 gene. This alteration results from a A to T substitution at nucleotide position 641, causing the histidine (H) at amino acid position 214 to be replaced by a leucine (L). 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	Uncertain	0.42
BayesDel_addAF	Benign	-0.071	T
BayesDel_noAF	Benign	-0.34
CADD	Uncertain	25
DANN	Benign	0.97
DEOGEN2	Uncertain	0.52	.;.;D;.
Eigen	Uncertain	0.63
Eigen_PC	Uncertain	0.66
FATHMM_MKL	Pathogenic	1.0	D
LIST_S2	Uncertain	0.93	D;T;T;T
M_CAP	Benign	0.020	T
MetaRNN	Uncertain	0.43	T;T;T;T
MetaSVM	Benign	-0.85	T
MutationAssessor	Benign	1.1	.;.;L;.
PrimateAI	Uncertain	0.73	T
PROVEAN	Benign	-1.9	.;.;N;N
REVEL	Benign	0.27
Sift	Uncertain	0.0050	.;.;D;D
Sift4G	Benign	0.081	T;T;D;T
Polyphen		0.98, 0.98	.;.;D;D
Vest4		0.46, 0.48
MutPred		0.57		.;.;Gain of stability (P = 0.0076);.;
MVP		0.33
MPC		0.82
ClinPred		0.76	D
GERP RS		5.3
Varity_R		0.45
gMVP		0.68

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: chr19-59058797;