19-57840915-A-T

Position:

• chr19-57840915-A-T

Variant summary

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

The NM_001376223.1(ZNF587B):​c.241A>T​(p.Thr81Ser) 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. 12/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 29)
• Consequence: ZNF587B NM_001376223.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.699

Genes affected

ZNF587B (HGNC:37142): (zinc finger protein 587B) Predicted to enable DNA-binding transcription repressor activity, RNA polymerase II-specific and RNA polymerase II transcription regulatory region sequence-specific DNA binding activity. Predicted to be involved in negative regulation of transcription by RNA polymerase II. Predicted to be located in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ENSG00000268750 (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=0.07161656).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNF587B	NM_001376223.1	c.241A>T	p.Thr81Ser	missense_variant	3/3	ENST00000594901.2	NP_001363152.1
ZNF587B	NM_001204818.2	c.241A>T	p.Thr81Ser	missense_variant	3/4		NP_001191747.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZNF587B	ENST00000594901.2	c.241A>T	p.Thr81Ser	missense_variant	3/3	4	NM_001376223.1	ENSP00000469623.1
ZNF587B	ENST00000442832.8	c.241A>T	p.Thr81Ser	missense_variant	3/4	2		ENSP00000392410.2
ENSG00000268750	ENST00000593873.6	c.34-17661A>T		intron_variant		4		ENSP00000469133.2

Frequencies

GnomAD3 genomes Cov.: 29

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 29

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 01, 2024

The c.241A>T (p.T81S) alteration is located in exon 3 (coding exon 3) of the ZNF587B gene. This alteration results from a A to T substitution at nucleotide position 241, causing the threonine (T) at amino acid position 81 to be replaced by a serine (S). 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	0.15
BayesDel_addAF	Benign	-0.38	T
BayesDel_noAF	Benign	-0.78
CADD	Benign	3.4
DANN	Benign	0.74
DEOGEN2	Benign	0.077	T;T;.
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.011	N
LIST_S2	Benign	0.41	T;T;T
M_CAP	Benign	0.0021	T
MetaRNN	Benign	0.072	T;T;T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	1.3	.;L;.
PROVEAN	Uncertain	-2.7	.;D;.
REVEL	Benign	0.026
Sift	Benign	0.076	.;T;.
Sift4G	Benign	0.097	T;D;T
Polyphen		0.13	.;B;.
Vest4		0.025, 0.077
MutPred		0.28		.;Gain of disorder (P = 0.0527);Gain of disorder (P = 0.0527);
MVP		0.067
MPC		0.31
ClinPred		0.084	T
GERP RS		1.0
Varity_R		0.021
gMVP		0.020

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: chr19-58352283;