19-12145469-G-C

Variant names:

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

Variant summary

Our verdict is Uncertain significance. Variant got 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. 11/18 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. 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

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 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=0.23735595).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZNF625	NM_145233.4	c.947C>G	p.Ser316Trp	missense_variant	Exon 4 of 4	ENST00000439556.3	NP_660276.2
ZNF625	NR_037801.2	n.1119C>G		non_coding_transcript_exon_variant	Exon 4 of 4
ZNF625-ZNF20	NR_037802.1	n.364+1926C>G		intron_variant	Intron 3 of 7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZNF625	ENST00000439556.3	c.947C>G	p.Ser316Trp	missense_variant	Exon 4 of 4	2	NM_145233.4	ENSP00000394380.2
ZNF625-ZNF20	ENST00000430024.5	n.191+1926C>G		intron_variant	Intron 3 of 7	5		ENSP00000457423.1

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

GnomAD3 exomes AF: 0.00000398 AC: 1 AN: 251458 Hom.: 0 AF XY: 0.00000736 AC XY: 1 AN XY: 135902

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 SAS 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

Gnomad4 AFR AF: 0.0000242

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000147

Gnomad4 OTH AF: 0.00

Bravo AF: 0.0000189

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
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
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

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

LitVar

Other links and lift over

dbSNP: rs778993312; hg19: chr19-12256284;