chr16-31885239-C-T

Variant names:

• chr16-31885239-C-T
• rs751086169
• NM_003414.6:c.209C>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_003414.6(ZNF267):​c.209C>T​(p.Thr70Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000275 in 1,454,908 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 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: 0.0000027 (0 hom.)
• Consequence: ZNF267 NM_003414.6 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.151
• Publications: 0 publications found

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

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=0.088410586).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003414.6. 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
	ZNF267	NM_003414.6	MANE Select	c.209C>T	p.Thr70Ile	missense	Exon 3 of 4	NP_003405.4
	ZNF267	NM_001265588.2		c.113C>T	p.Thr38Ile	missense	Exon 4 of 5	NP_001252517.2
	ZNF267	NR_049749.2		n.369C>T		non_coding_transcript_exon	Exon 3 of 5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZNF267	ENST00000300870.15	TSL:1 MANE Select	c.209C>T	p.Thr70Ile	missense	Exon 3 of 4	ENSP00000300870.10	Q14586
	ZNF267	ENST00000562971.1	TSL:4	c.113C>T	p.Thr38Ile	missense	Exon 3 of 4	ENSP00000455493.1	H3BPW2
	ZNF267	ENST00000394846.7	TSL:2	c.209C>T	p.Thr70Ile	missense	Exon 3 of 5	ENSP00000461286.1	I3L4I6

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD2 exomes AF: 0.0000160 AC: 4 AN: 250180 AF XY: 0.0000296

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000219

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000275 AC: 4 AN: 1454908 Hom.: 0 Cov.: 30 AF XY: 0.00000276 AC XY: 2 AN XY: 723928

African (AFR) AF: 0.00 AC: 0 AN: 33300

American (AMR) AF: 0.00 AC: 0 AN: 44524

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25954

East Asian (EAS) AF: 0.000101 AC: 4 AN: 39600

South Asian (SAS) AF: 0.00 AC: 0 AN: 85678

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53080

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4424

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1108456

Other (OTH) AF: 0.00 AC: 0 AN: 59892

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000113

ExAC AF: 0.00000824 AC: 1

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Benign	-0.48	T
BayesDel_noAF	Benign	-0.63
CADD	Benign	13
DANN	Benign	0.30
DEOGEN2	Benign	0.0081	T
Eigen	Benign	-0.50
Eigen_PC	Benign	-0.80
FATHMM_MKL	Benign	0.0085	N
LIST_S2	Benign	0.073	T
M_CAP	Benign	0.0011	T
MetaRNN	Benign	0.088	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.5	L
PhyloP100		-0.15
PrimateAI	Benign	0.45	T
PROVEAN	Benign	-0.65	N
REVEL	Benign	0.028
Sift	Benign	0.28	T
Sift4G	Benign	0.29	T
Polyphen		0.98	D
Vest4		0.23
MutPred		0.29		Loss of disorder (P = 0.0632)
MVP		0.40
MPC		0.15
ClinPred		0.065	T
GERP RS		0.47
RBP_binding_hub_radar		0.97
RBP_regulation_power_radar		2.1
Varity_R		0.077
gMVP		0.059
Mutation Taster		=99/1	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.060		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: rs751086169; hg19: chr16-31896560;