NM_006965.4:c.75A>T

Variant names:

• chr18-35340576-T-A
• rs1388694123
• NM_006965.4:c.75A>T

Variant summary

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

The NM_006965.4(ZNF24):​c.75A>T​(p.Arg25Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000131 in 152,214 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: 𝑓 0.000013 (0 hom., cov: 32)
• Consequence: ZNF24 NM_006965.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.716
• Publications: 0 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: 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=0.09008473).

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.75A>T	p.Arg25Ser	missense	Exon 2 of 4	NP_008896.2	P17028-1
	ZNF24	NM_001375815.1		c.75A>T	p.Arg25Ser	missense	Exon 2 of 4	NP_001362744.1	P17028-1
	ZNF24	NM_001308123.2		c.75A>T	p.Arg25Ser	missense	Exon 2 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.75A>T	p.Arg25Ser	missense	Exon 2 of 4	ENSP00000261332.5	P17028-1
	ZNF24	ENST00000399061.3	TSL:1	c.75A>T	p.Arg25Ser	missense	Exon 2 of 4	ENSP00000382015.2	P17028-1
	ZNF24	ENST00000589881.5	TSL:1	c.75A>T	p.Arg25Ser	missense	Exon 1 of 3	ENSP00000467655.1	P17028-2

Frequencies

GnomAD3 genomes AF: 0.0000131 AC: 2 AN: 152214 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000483

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: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome Cov.: 31

GnomAD4 genome AF: 0.0000131 AC: 2 AN: 152214 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 74366

African (AFR) AF: 0.0000483 AC: 2 AN: 41450

American (AMR) AF: 0.00 AC: 0 AN: 15288

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 5198

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

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10624

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

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68026

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

Alfa AF: 0.00 Hom.: 0

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	0.40
BayesDel_addAF	Benign	-0.15	T
BayesDel_noAF	Benign	-0.46
CADD	Benign	16
DANN	Benign	0.96
DEOGEN2	Benign	0.082	T
Eigen	Benign	-0.55
Eigen_PC	Benign	-0.42
FATHMM_MKL	Uncertain	0.87	D
LIST_S2	Benign	0.70	T
M_CAP	Benign	0.0037	T
MetaRNN	Benign	0.090	T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	1.6	L
PhyloP100		0.72
PrimateAI	Uncertain	0.63	T
PROVEAN	Benign	0.080	N
REVEL	Benign	0.15
Sift	Benign	0.73	T
Sift4G	Benign	0.63	T
Polyphen		0.056	B
Vest4		0.54
MutPred		0.33		Gain of phosphorylation at R25 (P = 0.0162)
MVP		0.42
MPC		0.71
ClinPred		0.24	T
GERP RS		1.7
PromoterAI		0.0044	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.063
gMVP		0.58
Mutation Taster		=86/14	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: rs1388694123; hg19: chr18-32920540;