chr19-44272967-C-T

Variant names:

• chr19-44272967-C-T
• NM_001207005.2:c.307C>T

Variant summary

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

The NM_001207005.2(ZNF233):​c.307C>T​(p.Leu103Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: ZNF233 NM_001207005.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.0410
• Publications: 0 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: 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=0.15191016).

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.307C>T	p.Leu103Phe	missense	Exon 5 of 5	NP_001193934.1	A6NK53
	ZNF233	NM_181756.3		c.307C>T	p.Leu103Phe	missense	Exon 5 of 5	NP_861421.2	A6NK53
	ZNF233	NM_001330529.2		c.*67C>T		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.307C>T	p.Leu103Phe	missense	Exon 5 of 5	ENSP00000507588.1	A6NK53
	ZNF235	ENST00000589799.5	TSL:1	c.238+25841G>A		intron	N/A	ENSP00000468695.1	K7ESF8
	ZNF233	ENST00000391958.6	TSL:2	c.307C>T	p.Leu103Phe	missense	Exon 5 of 5	ENSP00000375820.1	A6NK53

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

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	0.17
BayesDel_addAF	Benign	-0.28	T
BayesDel_noAF	Benign	-0.64
CADD	Benign	7.7
DANN	Uncertain	1.0
DEOGEN2	Benign	0.034	T
Eigen	Benign	-0.40
Eigen_PC	Benign	-0.65
FATHMM_MKL	Benign	0.030	N
LIST_S2	Benign	0.60	T
M_CAP	Benign	0.0020	T
MetaRNN	Benign	0.15	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	2.0	M
PhyloP100		0.041
PrimateAI	Benign	0.27	T
PROVEAN	Uncertain	-2.9	D
REVEL	Benign	0.024
Sift	Benign	0.034	D
Sift4G	Uncertain	0.052	T
Polyphen		0.96	D
Vest4		0.092
MutPred		0.40		Gain of loop (P = 0.1069)
MVP		0.15
MPC		0.18
ClinPred		0.68	D
GERP RS		0.17
Varity_R		0.11
gMVP		0.042
Mutation Taster		=96/4	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

hg19: chr19-44777120;