chr16-31914928-C-G

Variant names:

• chr16-31914928-C-G
• rs1390041028
• NM_003414.6:c.679C>G

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_003414.6(ZNF267):​c.679C>G​(p.Gln227Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000274 in 1,459,084 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000027 (0 hom.)
• Consequence: ZNF267 NM_003414.6 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -3.20

Genes affected

ZNF267 (HGNC:13060): (zinc finger protein 267) Predicted to enable DNA-binding transcription activator 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 by RNA polymerase II. Predicted to be active in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.065373).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZNF267	NM_003414.6	c.679C>G	p.Gln227Glu	missense_variant	Exon 4 of 4	ENST00000300870.15	NP_003405.4
ZNF267	NM_001265588.2	c.583C>G	p.Gln195Glu	missense_variant	Exon 5 of 5		NP_001252517.2
ZNF267	NR_049749.2	n.883C>G		non_coding_transcript_exon_variant	Exon 5 of 5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZNF267	ENST00000300870.15	c.679C>G	p.Gln227Glu	missense_variant	Exon 4 of 4	1	NM_003414.6	ENSP00000300870.10
ZNF267	ENST00000575471.2	n.3075C>G		non_coding_transcript_exon_variant	Exon 1 of 1	6
ZNF267	ENST00000394846.7	c.*489C>G		downstream_gene_variant		2		ENSP00000461286.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.00000407 AC: 1 AN: 245678 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 133154

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000551

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 AF: 0.00000274 AC: 4 AN: 1459084 Hom.: 0 Cov.: 30 AF XY: 0.00000276 AC XY: 2 AN XY: 725594

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000757

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.0000166

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Dec 14, 2021

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.679C>G (p.Q227E) alteration is located in exon 4 (coding exon 4) of the ZNF267 gene. This alteration results from a C to G substitution at nucleotide position 679, causing the glutamine (Q) at amino acid position 227 to be replaced by a glutamic acid (E). 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	0.068
BayesDel_addAF	Benign	-0.47	T
BayesDel_noAF	Benign	-0.74
CADD	Benign	1.5
DANN	Benign	0.42
DEOGEN2	Benign	0.013	T
Eigen	Benign	-1.3
Eigen_PC	Benign	-1.5
FATHMM_MKL	Benign	0.011	N
LIST_S2	Benign	0.079	T
M_CAP	Benign	0.00066	T
MetaRNN	Benign	0.065	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.5	L
PrimateAI	Benign	0.22	T
PROVEAN	Benign	-1.3	N
REVEL	Benign	0.0070
Sift	Benign	0.27	T
Sift4G	Benign	0.93	T
Polyphen		0.0080	B
Vest4		0.051
MutPred		0.19		Gain of phosphorylation at S230 (P = 0.0982);
MVP		0.085
MPC		0.23
ClinPred		0.043	T
GERP RS		-0.92
Varity_R		0.059
gMVP		0.0020

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: rs1390041028; hg19: chr16-31926249;