1-248847290-G-C

Position:

• chr1-248847290-G-C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_024836.3(ZNF672):​c.16G>C​(p.Gly6Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000138 in 1,449,640 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: ZNF672 NM_024836.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.79

Genes affected

ZNF672 (HGNC:26179): (zinc finger protein 672) Predicted to enable DNA-binding transcription factor activity, RNA polymerase II-specific and sequence-specific DNA binding activity. Predicted to be involved in regulation of transcription by RNA polymerase II. Located in nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

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=0.07572463).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNF672	NM_024836.3	c.16G>C	p.Gly6Arg	missense_variant	4/4	ENST00000306562.8	NP_079112.1
ZNF672	XM_005270336.3	c.16G>C	p.Gly6Arg	missense_variant	4/4		XP_005270393.1
ZNF672	XM_047430823.1	c.16G>C	p.Gly6Arg	missense_variant	4/4		XP_047286779.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZNF672	ENST00000306562.8	c.16G>C	p.Gly6Arg	missense_variant	4/4	1	NM_024836.3	ENSP00000421915	P1
ZNF672	ENST00000428515.5	c.16G>C	p.Gly6Arg	missense_variant	4/4	2		ENSP00000427021
ZNF672	ENST00000423362.1	c.16G>C	p.Gly6Arg	missense_variant	4/4	5		ENSP00000426199
ZNF672	ENST00000505503.5			downstream_gene_variant		3		ENSP00000422534

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000138 AC: 2 AN: 1449640 Hom.: 0 Cov.: 30 AF XY: 0.00000278 AC XY: 2 AN XY: 718182

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: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000182

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

Alfa AF: 0.0000251 Hom.: 0

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 30, 2023

The c.16G>C (p.G6R) alteration is located in exon 4 (coding exon 1) of the ZNF672 gene. This alteration results from a G to C substitution at nucleotide position 16, causing the glycine (G) at amino acid position 6 to be replaced by an arginine (R). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.21
BayesDel_addAF	Benign	-0.24	T
BayesDel_noAF	Benign	-0.58
CADD	Benign	10
DANN	Benign	0.70
DEOGEN2	Benign	0.0079	T;.;T
Eigen	Benign	-0.91
Eigen_PC	Benign	-0.95
FATHMM_MKL	Benign	0.30	N
LIST_S2	Benign	0.49	T;T;T
M_CAP	Benign	0.012	T
MetaRNN	Benign	0.076	T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-1.1	N;.;.
MutationTaster	Benign	1.0	N
PrimateAI	Uncertain	0.56	T
PROVEAN	Benign	1.1	N;N;N
REVEL	Benign	0.084
Sift	Uncertain	0.021	D;T;D
Sift4G	Benign	0.18	T;D;T
Polyphen		0.39	B;.;.
Vest4		0.099
MutPred		0.33		Gain of MoRF binding (P = 0.0056);Gain of MoRF binding (P = 0.0056);Gain of MoRF binding (P = 0.0056);
MVP		0.13
MPC		0.93
ClinPred		0.14	T
GERP RS		2.5
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.067
gMVP		0.10

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.080		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: rs576263422; hg19: chr1-249141489;