NM_006965.4:c.733C>T

Variant names:

• chr18-35337606-G-A
• rs142376346
• NM_006965.4:c.733C>T

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_006965.4(ZNF24):​c.733C>T​(p.Pro245Ser) variant causes a missense change. The variant allele was found at a frequency of 0.000638 in 1,614,082 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P245T) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.00050 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00065 (0 hom.)
• Consequence: ZNF24 NM_006965.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.45
• Publications: 7 publications found

Genes affected

ZNF24 (HGNC:13032): (zinc finger protein 24) Enables DNA-binding transcription activator activity, RNA polymerase II-specific; identical protein binding activity; and sequence-specific DNA binding activity. Involved in negative regulation of transcription, DNA-templated and positive regulation of transcription by RNA polymerase II. Located in nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.037519693).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006965.4. 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
	ZNF24	NM_006965.4	MANE Select	c.733C>T	p.Pro245Ser	missense	Exon 4 of 4	NP_008896.2	P17028-1
	ZNF24	NM_001375815.1		c.733C>T	p.Pro245Ser	missense	Exon 4 of 4	NP_001362744.1	P17028-1
	ZNF24	NM_001308123.2		c.*1454C>T		3_prime_UTR	Exon 4 of 4	NP_001295052.1	P17028-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZNF24	ENST00000261332.11	TSL:1 MANE Select	c.733C>T	p.Pro245Ser	missense	Exon 4 of 4	ENSP00000261332.5	P17028-1
	ZNF24	ENST00000399061.3	TSL:1	c.733C>T	p.Pro245Ser	missense	Exon 4 of 4	ENSP00000382015.2	P17028-1
	ZNF24	ENST00000589881.5	TSL:1	c.*1454C>T		3_prime_UTR	Exon 3 of 3	ENSP00000467655.1	P17028-2

Frequencies

GnomAD3 genomes AF: 0.000499 AC: 76 AN: 152178 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000241

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000916

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.0000942

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000706

Gnomad OTH AF: 0.00144

GnomAD2 exomes AF: 0.000462 AC: 116 AN: 251138 AF XY: 0.000508

Gnomad AFR exome AF: 0.000246

Gnomad AMR exome AF: 0.000723

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000714

Gnomad OTH exome AF: 0.000980

GnomAD4 exome AF: 0.000653 AC: 954 AN: 1461786 Hom.: 0 Cov.: 36 AF XY: 0.000664 AC XY: 483 AN XY: 727198

African (AFR) AF: 0.000149 AC: 5 AN: 33478

American (AMR) AF: 0.000760 AC: 34 AN: 44720

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26132

East Asian (EAS) AF: 0.00 AC: 0 AN: 39694

South Asian (SAS) AF: 0.0000116 AC: 1 AN: 86256

European-Finnish (FIN) AF: 0.0000375 AC: 2 AN: 53390

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.000788 AC: 876 AN: 1111956

Other (OTH) AF: 0.000596 AC: 36 AN: 60392

GnomAD4 genome AF: 0.000499 AC: 76 AN: 152296 Hom.: 0 Cov.: 32 AF XY: 0.000443 AC XY: 33 AN XY: 74464

African (AFR) AF: 0.000241 AC: 10 AN: 41562

American (AMR) AF: 0.000915 AC: 14 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5188

South Asian (SAS) AF: 0.00 AC: 0 AN: 4826

European-Finnish (FIN) AF: 0.0000942 AC: 1 AN: 10618

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000706 AC: 48 AN: 68024

Other (OTH) AF: 0.00142 AC: 3 AN: 2108

Alfa AF: 0.000704 Hom.: 0

Bravo AF: 0.000506

TwinsUK AF: 0.000809 AC: 3

ALSPAC AF: 0.00182 AC: 7

ESP6500AA AF: 0.000454 AC: 2

ESP6500EA AF: 0.000465 AC: 4

ExAC AF: 0.000445 AC: 54

EpiCase AF: 0.000654

EpiControl AF: 0.000711

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	0.12
BayesDel_addAF	Benign	-0.45	T
BayesDel_noAF	Benign	-0.43
CADD	Benign	23
DANN	Benign	0.97
DEOGEN2	Benign	0.11	T
Eigen	Uncertain	0.40
Eigen_PC	Uncertain	0.48
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Benign	0.013	T
M_CAP	Benign	0.0067	T
MetaRNN	Benign	0.038	T
MetaSVM	Benign	-0.90	T
MutationAssessor	Benign	1.1	L
PhyloP100		5.4
PrimateAI	Uncertain	0.54	T
PROVEAN	Benign	-1.9	N
REVEL	Benign	0.13
Sift	Benign	0.43	T
Sift4G	Benign	0.51	T
Polyphen		0.96	D
Vest4		0.36
MVP		0.15
MPC		1.0
ClinPred		0.047	T
GERP RS		5.3
Varity_R		0.10
gMVP		0.50
Mutation Taster		=59/41	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: rs142376346; hg19: chr18-32917570; COSMIC: COSV54348551; COSMIC: COSV54348551;