18-35337626-C-T

Variant names:

• chr18-35337626-C-T
• rs750561326
• NM_006965.4:c.713G>A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_006965.4(ZNF24):​c.713G>A​(p.Arg238Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000958 in 1,461,794 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R238T) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000096 (0 hom.)
• Consequence: ZNF24 NM_006965.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.76

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

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.11496243).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZNF24	NM_006965.4	c.713G>A	p.Arg238Lys	missense_variant	Exon 4 of 4	ENST00000261332.11	NP_008896.2
ZNF24	NM_001375815.1	c.713G>A	p.Arg238Lys	missense_variant	Exon 4 of 4		NP_001362744.1
ZNF24	NM_001308123.2	c.*1434G>A		3_prime_UTR_variant	Exon 4 of 4		NP_001295052.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZNF24	ENST00000261332.11	c.713G>A	p.Arg238Lys	missense_variant	Exon 4 of 4	1	NM_006965.4	ENSP00000261332.5
ZNF24	ENST00000399061.3	c.713G>A	p.Arg238Lys	missense_variant	Exon 4 of 4	1		ENSP00000382015.2
ZNF24	ENST00000589881	c.*1434G>A		3_prime_UTR_variant	Exon 3 of 3	1		ENSP00000467655.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.0000199 AC: 5 AN: 251104 Hom.: 0 AF XY: 0.0000221 AC XY: 3 AN XY: 135716

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000578

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000980

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000958 AC: 14 AN: 1461794 Hom.: 0 Cov.: 36 AF XY: 0.0000110 AC XY: 8 AN XY: 727198

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.0000447

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000139

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ExAC AF: 0.0000330 AC: 4

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Benign	-0.30	T
BayesDel_noAF	Benign	-0.47
CADD	Benign	19
DANN	Benign	0.96
DEOGEN2	Benign	0.079	T;T
Eigen	Benign	-0.11
Eigen_PC	Benign	-0.025
FATHMM_MKL	Benign	0.28	N
LIST_S2	Benign	0.15	.;T
M_CAP	Benign	0.0038	T
MetaRNN	Benign	0.11	T;T
MetaSVM	Benign	-0.91	T
MutationAssessor	Benign	1.4	L;L
PrimateAI	Uncertain	0.49	T
PROVEAN	Benign	-1.4	N;N
REVEL	Benign	0.11
Sift	Benign	0.28	T;T
Sift4G	Benign	0.41	T;T
Polyphen		0.83	P;P
Vest4		0.39
MutPred		0.47		Gain of methylation at R238 (P = 0.013);Gain of methylation at R238 (P = 0.013);
MVP		0.30
MPC		0.53
ClinPred		0.36	T
GERP RS		4.5
Varity_R		0.11
gMVP		0.50

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

Publications

LitVar

Other links and lift over

dbSNP: rs750561326; hg19: chr18-32917590;