chr1-227654555-G-A

Position:

• chr1-227654555-G-A

Variant summary

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

The ENST00000343776.10(ZNF678):​c.305G>A​(p.Cys102Tyr) variant causes a missense change. The variant allele was found at a frequency of 0.000000684 in 1,461,196 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: ZNF678 ENST00000343776.10 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.15

Genes affected

ZNF678 (HGNC:28652): (zinc finger protein 678) Predicted to enable DNA-binding transcription factor activity, RNA polymerase II-specific and RNA polymerase II cis-regulatory region sequence-specific DNA binding activity. Predicted to be involved in regulation of transcription, DNA-templated. Predicted to be located in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNF678	NM_001367909.1	c.305G>A	p.Cys102Tyr	missense_variant	4/4	ENST00000343776.10	NP_001354838.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZNF678	ENST00000343776.10	c.305G>A	p.Cys102Tyr	missense_variant	4/4	1	NM_001367909.1	ENSP00000344828	P1
ZNF678	ENST00000397097.4	c.305G>A	p.Cys102Tyr	missense_variant	2/2	1		ENSP00000440403	P1
ZNF678	ENST00000608949.5	c.226+79G>A		intron_variant		1		ENSP00000477097
ZNF678	ENST00000440339.1	c.470G>A	p.Cys157Tyr	missense_variant	4/4	2		ENSP00000394651

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461196 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 726904

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: 9.00e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

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

Jan 04, 2024

The c.470G>A (p.C157Y) alteration is located in exon 4 (coding exon 4) of the ZNF678 gene. This alteration results from a G to A substitution at nucleotide position 470, causing the cysteine (C) at amino acid position 157 to be replaced by a tyrosine (Y). 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	Pathogenic	0.70
BayesDel_addAF	Benign	-0.097	T
BayesDel_noAF	Benign	-0.38
CADD	Benign	12
DANN	Benign	0.52
DEOGEN2	Benign	0.25	T;.;T
Eigen	Benign	-1.0
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.00034	N
LIST_S2	Benign	0.53	.;T;T
M_CAP	Benign	0.011	T
MetaRNN	Uncertain	0.62	D;D;D
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-0.42	N;.;N
MutationTaster	Benign	1.0	N;N
PrimateAI	Uncertain	0.53	T
PROVEAN	Uncertain	-2.6	D;D;.
REVEL	Benign	0.25
Sift	Benign	0.22	T;T;.
Sift4G	Benign	0.15	T;D;T
Polyphen		0.47	P;.;P
Vest4		0.19
MutPred		0.87		Gain of MoRF binding (P = 0.0709);.;Gain of MoRF binding (P = 0.0709);
MVP		0.095
MPC		0.034
ClinPred		0.30	T
GERP RS		-2.3
Varity_R		0.14
gMVP		0.055

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr1-227842256;