18-35339936-T-C

Variant names:

• chr18-35339936-T-C
• NM_006965.4:c.461A>G

Variant summary

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

The NM_006965.4(ZNF24):​c.461A>G​(p.Asp154Gly) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: ZNF24 NM_006965.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.85

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=0.0841527).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZNF24	NM_006965.4	c.461A>G	p.Asp154Gly	missense_variant	Exon 3 of 4	ENST00000261332.11	NP_008896.2
ZNF24	NM_001375815.1	c.461A>G	p.Asp154Gly	missense_variant	Exon 3 of 4		NP_001362744.1
ZNF24	NM_001308123.2	c.461A>G	p.Asp154Gly	missense_variant	Exon 3 of 4		NP_001295052.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZNF24	ENST00000261332.11	c.461A>G	p.Asp154Gly	missense_variant	Exon 3 of 4	1	NM_006965.4	ENSP00000261332.5
ZNF24	ENST00000399061.3	c.461A>G	p.Asp154Gly	missense_variant	Exon 3 of 4	1		ENSP00000382015.2
ZNF24	ENST00000589881.5	c.461A>G	p.Asp154Gly	missense_variant	Exon 2 of 3	1		ENSP00000467655.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Dec 10, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.461A>G (p.D154G) alteration is located in exon 3 (coding exon 2) of the ZNF24 gene. This alteration results from a A to G substitution at nucleotide position 461, causing the aspartic acid (D) at amino acid position 154 to be replaced by a glycine (G). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.29
BayesDel_addAF	Benign	-0.22	T
BayesDel_noAF	Benign	-0.55
CADD	Uncertain	23
DANN	Uncertain	0.98
DEOGEN2	Benign	0.21	T;.;T
Eigen	Benign	-0.59
Eigen_PC	Benign	-0.46
FATHMM_MKL	Benign	0.67	D
LIST_S2	Benign	0.14	.;T;T
M_CAP	Benign	0.0038	T
MetaRNN	Benign	0.084	T;T;T
MetaSVM	Benign	-0.97	T
MutationAssessor	Benign	0.69	N;N;N
PrimateAI	Uncertain	0.49	T
PROVEAN	Uncertain	-2.8	D;.;D
REVEL	Benign	0.080
Sift	Benign	0.056	T;.;T
Sift4G	Benign	0.17	T;T;T
Polyphen		0.0	B;B;B
Vest4		0.28
MutPred		0.37		Loss of stability (P = 0.0182);Loss of stability (P = 0.0182);Loss of stability (P = 0.0182);
MVP		0.12
MPC		0.62
ClinPred		0.21	T
GERP RS		4.4
Varity_R		0.15
gMVP		0.47

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr18-32919900;