19-12147441-C-T

Variant names:

• chr19-12147441-C-T
• rs144252279
• NM_145233.4:c.145G>A

Variant summary

Our verdict is Uncertain significance. The variant received 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. 13/20 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
• Publications: 0 publications found

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:48368): (ZNF625-ZNF20 readthrough (NMD candidate)) This locus represents naturally occurring read-through transcription between the neighboring zinc finger protein 625 (ZNF625) and zinc finger protein 20 (ZNF20) genes on chromosome 19. The read-through transcript is a candidate for nonsense-mediated mRNA decay (NMD), and is thus unlikely to produce a protein product. [provided by RefSeq, Feb 2011]

ENSG00000290812 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.08420253).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_145233.4. 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
	ZNF625	NM_145233.4	MANE Select	c.145G>A	p.Asp49Asn	missense	Exon 3 of 4	NP_660276.2	Q96I27-2
	ZNF625	NR_037801.2		n.317G>A		non_coding_transcript_exon	Exon 3 of 4
	ZNF625-ZNF20	NR_037802.1		n.318G>A		non_coding_transcript_exon	Exon 3 of 8

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZNF625	ENST00000439556.3	TSL:2 MANE Select	c.145G>A	p.Asp49Asn	missense	Exon 3 of 4	ENSP00000394380.2	Q96I27-2
	ZNF625	ENST00000455799.1	TSL:1	c.141G>A	p.Lys47Lys	synonymous	Exon 3 of 4	ENSP00000398518.1	F2Z3I2
	ZNF625-ZNF20	ENST00000430024.5	TSL:5	n.145G>A		non_coding_transcript_exon	Exon 3 of 8	ENSP00000457423.1	F8WDT6

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

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	0.19
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
M_CAP	Benign	0.0015	T
MetaRNN	Benign	0.084	T
MetaSVM	Benign	-0.90	T
PhyloP100		0.067
PrimateAI	Benign	0.36	T
PROVEAN	Uncertain	-3.4	D
REVEL	Benign	0.032
Sift	Benign	0.24	T
Sift4G	Uncertain	0.039	D
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
PromoterAI		0.0087	Neutral
gMVP		0.015
Mutation Taster		=299/1	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: rs144252279; hg19: chr19-12258256;