19-12147441-C-T

Position:

• chr19-12147441-C-T

Variant summary

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

The NM_145233.4(ZNF625):​c.145G>A​(p.Asp49Asn) 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. 11/18 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: ZNF625 NM_145233.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.0670

Genes affected

ZNF625 (HGNC:30571): (zinc finger protein 625) Predicted to enable DNA-binding transcription factor activity, RNA polymerase II-specific and RNA polymerase II transcription regulatory region sequence-specific DNA binding activity. Predicted to be involved in regulation of transcription by RNA polymerase II. Predicted to be active in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ZNF625-ZNF20 (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=0.08420253).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNF625	NM_145233.4	c.145G>A	p.Asp49Asn	missense_variant	3/4	ENST00000439556.3	NP_660276.2
ZNF625-ZNF20	NR_037802.1	n.318G>A		non_coding_transcript_exon_variant	3/8
ZNF625	NR_037801.2	n.317G>A		non_coding_transcript_exon_variant	3/4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZNF625	ENST00000439556.3	c.145G>A	p.Asp49Asn	missense_variant	3/4	2	NM_145233.4	ENSP00000394380	P1
ZNF625	ENST00000455799.1	c.141G>A	p.Lys47=	synonymous_variant	3/4	1		ENSP00000398518
ZNF625	ENST00000414892.5	c.142G>A	p.Asp48Asn	missense_variant	2/4	5		ENSP00000405156

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

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

Dec 21, 2023

The c.145G>A (p.D49N) alteration is located in exon 3 (coding exon 3) of the ZNF625 gene. This alteration results from a G to A substitution at nucleotide position 145, causing the aspartic acid (D) at amino acid position 49 to be replaced by an asparagine (N). 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
BayesDel_addAF	Benign	-0.37	T
BayesDel_noAF	Benign	-0.76
CADD	Benign	13
DANN	Uncertain	1.0
Eigen	Benign	-0.57
Eigen_PC	Benign	-0.77
FATHMM_MKL	Benign	0.0060	N
LIST_S2	Benign	0.45	T;T
M_CAP	Benign	0.0015	T
MetaRNN	Benign	0.084	T;T
MetaSVM	Benign	-0.90	T
MutationTaster	Benign	1.0	N;N;N;N
PrimateAI	Benign	0.36	T
PROVEAN	Uncertain	-3.4	D;D
REVEL	Benign	0.032
Sift	Benign	0.24	T;T
Sift4G	Uncertain	0.039	D;T
Vest4		0.14
MutPred		0.34		.;Gain of MoRF binding (P = 0.0594);
MVP		0.088
MPC		0.60
ClinPred		0.24	T
GERP RS		0.47
gMVP		0.015

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: chr19-12258256;