19-12146186-T-C

Variant names:

• chr19-12146186-T-C
• rs749584574
• NM_145233.4:c.230A>G

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_145233.4(ZNF625):​c.230A>G​(p.Asp77Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000889 in 1,461,838 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/18 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. D77V) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000089 (0 hom.)
• Consequence: ZNF625 NM_145233.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.31

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]

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.03755316).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZNF625	NM_145233.4	c.230A>G	p.Asp77Gly	missense_variant	Exon 4 of 4	ENST00000439556.3	NP_660276.2
ZNF625	NR_037801.2	n.402A>G		non_coding_transcript_exon_variant	Exon 4 of 4
ZNF625-ZNF20	NR_037802.1	n.364+1209A>G		intron_variant	Intron 3 of 7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZNF625	ENST00000439556.3	c.230A>G	p.Asp77Gly	missense_variant	Exon 4 of 4	2	NM_145233.4	ENSP00000394380.2
ZNF625-ZNF20	ENST00000430024.5	n.191+1209A>G		intron_variant	Intron 3 of 7	5		ENSP00000457423.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.0000120 AC: 3 AN: 250676 Hom.: 0 AF XY: 0.0000221 AC XY: 3 AN XY: 135826

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000980

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000889 AC: 13 AN: 1461838 Hom.: 0 Cov.: 34 AF XY: 0.0000124 AC XY: 9 AN XY: 727220

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000116

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000180

Gnomad4 OTH exome AF: 0.0000166

GnomAD4 genome Cov.: 32

ExAC AF: 0.0000165 AC: 2

Asia WGS AF: 0.000289 AC: 1 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Benign	-0.59	T
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.034
DANN	Benign	0.71
Eigen	Benign	-1.7
Eigen_PC	Benign	-1.8
FATHMM_MKL	Benign	0.0012	N
LIST_S2	Benign	0.032	T
M_CAP	Benign	0.00054	T
MetaRNN	Benign	0.038	T
MetaSVM	Benign	-0.96	T
PrimateAI	Benign	0.28	T
PROVEAN	Benign	0.29	N
REVEL	Benign	0.0070
Sift	Benign	1.0	T
Sift4G	Benign	1.0	T
Vest4		0.053
MVP		0.014
MPC		0.66
ClinPred		0.041	T
GERP RS		-1.7
gMVP		0.084

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs749584574; hg19: chr19-12257001;