19-12145469-G-C

Variant names:

• chr19-12145469-G-C
• rs778993312
• NM_145233.4:c.947C>G

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.947C>G​(p.Ser316Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000132 in 151,804 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/20 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. S316L) has been classified as Uncertain significance.

• Frequency: Genomes: 𝑓 0.000013 (0 hom., cov: 32)
• Consequence: ZNF625 NM_145233.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.211
• Publications: 1 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=0.23735595).

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.947C>G	p.Ser316Trp	missense	Exon 4 of 4	NP_660276.2	Q96I27-2
	ZNF625	NR_037801.2		n.1119C>G		non_coding_transcript_exon	Exon 4 of 4
	ZNF625-ZNF20	NR_037802.1		n.364+1926C>G		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZNF625	ENST00000439556.3	TSL:2 MANE Select	c.947C>G	p.Ser316Trp	missense	Exon 4 of 4	ENSP00000394380.2	Q96I27-2
	ZNF625	ENST00000455799.1	TSL:1	c.*757C>G		3_prime_UTR	Exon 4 of 4	ENSP00000398518.1	F2Z3I2
	ZNF625-ZNF20	ENST00000430024.5	TSL:5	n.191+1926C>G		intron	N/A	ENSP00000457423.1	F8WDT6

Frequencies

GnomAD3 genomes AF: 0.0000132 AC: 2 AN: 151804 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000242

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.00000398 AC: 1 AN: 251458 AF XY: 0.00000736

Gnomad AFR exome AF: 0.0000615

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome Cov.: 29

GnomAD4 genome AF: 0.0000132 AC: 2 AN: 151804 Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1 AN XY: 74112

African (AFR) AF: 0.0000242 AC: 1 AN: 41316

American (AMR) AF: 0.00 AC: 0 AN: 15230

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5160

South Asian (SAS) AF: 0.00 AC: 0 AN: 4802

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10556

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 310

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 67958

Other (OTH) AF: 0.00 AC: 0 AN: 2088

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000189

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.80
BayesDel_addAF	Benign	-0.32	T
BayesDel_noAF	Benign	-0.52
CADD	Benign	17
DANN	Uncertain	0.99
Eigen	Benign	-0.39
Eigen_PC	Benign	-0.72
FATHMM_MKL	Benign	0.024	N
LIST_S2	Benign	0.82	T
M_CAP	Benign	0.0039	T
MetaRNN	Benign	0.24	T
MetaSVM	Benign	-1.1	T
PhyloP100		-0.21
PrimateAI	Benign	0.37	T
PROVEAN	Pathogenic	-5.7	D
REVEL	Benign	0.053
Sift	Uncertain	0.0020	D
Sift4G	Uncertain	0.0040	D
Vest4		0.32
MVP		0.28
MPC		1.7
ClinPred		0.98	D
GERP RS		-0.40
gMVP		0.022
Mutation Taster		=98/2	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: rs778993312; hg19: chr19-12256284;