NM_001207005.2:c.311T>C

Variant names:

• chr19-44272971-T-C
• rs749598453
• NM_001207005.2:c.311T>C

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_001207005.2(ZNF233):​c.311T>C​(p.Ile104Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00012 in 1,613,256 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000020 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00013 (0 hom.)
• Consequence: ZNF233 NM_001207005.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -2.92
• Publications: 1 publications found

Genes affected

ZNF233 (HGNC:30946): (zinc finger protein 233) 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 by RNA polymerase II. Predicted to be active in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ZNF235 (HGNC:12866): (zinc finger protein 235) This gene product belongs to the zinc finger protein superfamily, members of which are regulatory proteins characterized by nucleic acid-binding zinc finger domains. The encoded protein is a member of the Kruppel family of zinc finger proteins, and contains Kruppel-associated box (KRAB) A and B domains and 15 tandemly arrayed C2H2-type zinc fingers. It is an ortholog of the mouse Zfp93 protein. This gene is located in a cluster of zinc finger genes on 19q13.2. [provided by RefSeq, Jul 2008]

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.07972491).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001207005.2. 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
	ZNF233	NM_001207005.2	MANE Select	c.311T>C	p.Ile104Thr	missense	Exon 5 of 5	NP_001193934.1	A6NK53
	ZNF233	NM_181756.3		c.311T>C	p.Ile104Thr	missense	Exon 5 of 5	NP_861421.2	A6NK53
	ZNF233	NM_001330529.2		c.*71T>C		3_prime_UTR	Exon 5 of 5	NP_001317458.1	K7ER86

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZNF233	ENST00000683810.1	MANE Select	c.311T>C	p.Ile104Thr	missense	Exon 5 of 5	ENSP00000507588.1	A6NK53
	ZNF235	ENST00000589799.5	TSL:1	c.238+25837A>G		intron	N/A	ENSP00000468695.1	K7ESF8
	ZNF233	ENST00000391958.6	TSL:2	c.311T>C	p.Ile104Thr	missense	Exon 5 of 5	ENSP00000375820.1	A6NK53

Frequencies

GnomAD3 genomes AF: 0.0000197 AC: 3 AN: 152234 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

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: 0.0000441

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000320 AC: 8 AN: 250102 AF XY: 0.0000295

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000705

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.000131 AC: 191 AN: 1461022 Hom.: 0 Cov.: 30 AF XY: 0.000132 AC XY: 96 AN XY: 726830

African (AFR) AF: 0.00 AC: 0 AN: 33474

American (AMR) AF: 0.00 AC: 0 AN: 44682

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26126

East Asian (EAS) AF: 0.00 AC: 0 AN: 39682

South Asian (SAS) AF: 0.00 AC: 0 AN: 86172

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52858

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5766

European-Non Finnish (NFE) AF: 0.000157 AC: 175 AN: 1111886

Other (OTH) AF: 0.000265 AC: 16 AN: 60376

GnomAD4 genome AF: 0.0000197 AC: 3 AN: 152234 Hom.: 0 Cov.: 32 AF XY: 0.0000269 AC XY: 2 AN XY: 74378

African (AFR) AF: 0.00 AC: 0 AN: 41454

American (AMR) AF: 0.00 AC: 0 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5200

South Asian (SAS) AF: 0.00 AC: 0 AN: 4836

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10620

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000441 AC: 3 AN: 68042

Other (OTH) AF: 0.00 AC: 0 AN: 2092

Alfa AF: 0.000112 Hom.: 0

Bravo AF: 0.0000264

ExAC AF: 0.0000330 AC: 4

EpiCase AF: 0.000109

EpiControl AF: 0.000178

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	Uncertain	0.35
BayesDel_addAF	Benign	-0.50	T
BayesDel_noAF	Benign	-0.76
CADD	Benign	0.64
DANN	Benign	0.89
DEOGEN2	Benign	0.0010	T
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.0072	N
LIST_S2	Benign	0.26	T
M_CAP	Benign	0.0019	T
MetaRNN	Benign	0.080	T
MetaSVM	Benign	-0.91	T
MutationAssessor	Benign	0.90	L
PhyloP100		-2.9
PrimateAI	Benign	0.35	T
PROVEAN	Benign	1.0	N
REVEL	Benign	0.0050
Sift	Benign	0.095	T
Sift4G	Benign	0.21	T
Polyphen		0.067	B
Vest4		0.031
MVP		0.048
MPC		0.098
ClinPred		0.054	T
GERP RS		0.29
Varity_R		0.034
gMVP		0.082
Mutation Taster		=100/0	polymorphism

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

Other links and lift over

dbSNP: rs749598453; hg19: chr19-44777124;