19-12145543-T-G

Variant names:

• chr19-12145543-T-G
• rs12972621
• NM_145233.4:c.873A>C

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_145233.4(ZNF625):​c.873A>C​(p.Arg291Arg) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.449 in 1,613,760 control chromosomes in the GnomAD database, including 170,466 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.36 (12041 hom., cov: 31)
  • Exomes 𝑓: 0.46 (158425 hom.)
• Consequence: ZNF625 NM_145233.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.569
• Publications: 16 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: Benign. The variant received -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BP7: Synonymous conserved (PhyloP=0.569 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.606 is higher than 0.05.

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.873A>C	p.Arg291Arg	synonymous	Exon 4 of 4	NP_660276.2	Q96I27-2
	ZNF625	NR_037801.2		n.1045A>C		non_coding_transcript_exon	Exon 4 of 4
	ZNF625-ZNF20	NR_037802.1		n.364+1852A>C		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZNF625	ENST00000439556.3	TSL:2 MANE Select	c.873A>C	p.Arg291Arg	synonymous	Exon 4 of 4	ENSP00000394380.2	Q96I27-2
	ZNF625	ENST00000455799.1	TSL:1	c.*683A>C		3_prime_UTR	Exon 4 of 4	ENSP00000398518.1	F2Z3I2
	ZNF625-ZNF20	ENST00000430024.5	TSL:5	n.191+1852A>C		intron	N/A	ENSP00000457423.1	F8WDT6

Frequencies

GnomAD3 genomes AF: 0.359 AC: 54447 AN: 151784 Hom.: 12042 Cov.: 31

Gnomad AFR AF: 0.0885

Gnomad AMI AF: 0.342

Gnomad AMR AF: 0.368

Gnomad ASJ AF: 0.451

Gnomad EAS AF: 0.625

Gnomad SAS AF: 0.596

Gnomad FIN AF: 0.478

Gnomad MID AF: 0.417

Gnomad NFE AF: 0.460

Gnomad OTH AF: 0.394

GnomAD2 exomes AF: 0.446 AC: 112113 AN: 251424 AF XY: 0.464

Gnomad AFR exome AF: 0.0802

Gnomad AMR exome AF: 0.324

Gnomad ASJ exome AF: 0.451

Gnomad EAS exome AF: 0.615

Gnomad FIN exome AF: 0.471

Gnomad NFE exome AF: 0.463

Gnomad OTH exome AF: 0.463

GnomAD4 exome AF: 0.459 AC: 670572 AN: 1461858 Hom.: 158425 Cov.: 65 AF XY: 0.465 AC XY: 337845 AN XY: 727228

African (AFR) AF: 0.0719 AC: 2407 AN: 33480

American (AMR) AF: 0.331 AC: 14823 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.458 AC: 11965 AN: 26136

East Asian (EAS) AF: 0.608 AC: 24134 AN: 39700

South Asian (SAS) AF: 0.586 AC: 50508 AN: 86256

European-Finnish (FIN) AF: 0.467 AC: 24955 AN: 53416

Middle Eastern (MID) AF: 0.465 AC: 2682 AN: 5768

European-Non Finnish (NFE) AF: 0.460 AC: 511577 AN: 1111984

Other (OTH) AF: 0.456 AC: 27521 AN: 60396

GnomAD4 genome AF: 0.358 AC: 54447 AN: 151902 Hom.: 12041 Cov.: 31 AF XY: 0.365 AC XY: 27116 AN XY: 74206

African (AFR) AF: 0.0883 AC: 3663 AN: 41478

American (AMR) AF: 0.368 AC: 5600 AN: 15234

Ashkenazi Jewish (ASJ) AF: 0.451 AC: 1563 AN: 3464

East Asian (EAS) AF: 0.624 AC: 3218 AN: 5156

South Asian (SAS) AF: 0.597 AC: 2876 AN: 4816

European-Finnish (FIN) AF: 0.478 AC: 5037 AN: 10528

Middle Eastern (MID) AF: 0.421 AC: 123 AN: 292

European-Non Finnish (NFE) AF: 0.460 AC: 31219 AN: 67914

Other (OTH) AF: 0.397 AC: 837 AN: 2110

Alfa AF: 0.425 Hom.: 22394

Bravo AF: 0.334

EpiCase AF: 0.475

EpiControl AF: 0.468

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	5.0
DANN	Benign	0.90
PhyloP100		0.57
Mutation Taster		=100/0	polymorphism (auto)

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: rs12972621; hg19: chr19-12256358; COSMIC: COSV63241434; COSMIC: COSV63241434;