10-43644213-G-C

Variant names:

• chr10-43644213-G-C
• rs1839201894
• NM_006973.3:c.659C>G

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_006973.3(ZNF32):​c.659C>G​(p.Thr220Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000041 in 1,461,882 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000041 (0 hom.)
• Consequence: ZNF32 NM_006973.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.0540

Genes affected

ZNF32 (HGNC:13095): (zinc finger protein 32) Enables sequence-specific double-stranded DNA binding activity. Predicted to be involved in regulation of transcription by RNA polymerase II. Predicted to be located in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ZNF32-AS3 (HGNC:):

ZNF32-AS1 (HGNC:23577): (ZNF32 antisense RNA 1)

ZNF32-AS3 (HGNC:23583): (ZNF32 antisense RNA 3)

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.039820194).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZNF32	NM_006973.3	c.659C>G	p.Thr220Ser	missense_variant	Exon 3 of 3	ENST00000374433.7	NP_008904.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZNF32	ENST00000374433.7	c.659C>G	p.Thr220Ser	missense_variant	Exon 3 of 3	1	NM_006973.3	ENSP00000363556.2
ZNF32-AS3	ENST00000458063.1	n.162+15235G>C		intron_variant	Intron 1 of 4	1
ZNF32	ENST00000395797.1	c.659C>G	p.Thr220Ser	missense_variant	Exon 3 of 3	2		ENSP00000379143.1
ZNF32-AS1	ENST00000453284.1	n.236+106G>C		intron_variant	Intron 1 of 1	5

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000410 AC: 6 AN: 1461882 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 727240

Gnomad4 AFR exome AF: 0.0000299

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000360

Gnomad4 OTH exome AF: 0.0000166

GnomAD4 genome Cov.: 33

Bravo AF: 0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Jan 09, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.659C>G (p.T220S) alteration is located in exon 3 (coding exon 2) of the ZNF32 gene. This alteration results from a C to G substitution at nucleotide position 659, causing the threonine (T) at amino acid position 220 to be replaced by a serine (S). 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	0.083
BayesDel_addAF	Benign	-0.35	T
BayesDel_noAF	Benign	-0.74
CADD	Benign	12
DANN	Benign	0.92
DEOGEN2	Benign	0.025	T;T
Eigen	Benign	-0.76
Eigen_PC	Benign	-0.61
FATHMM_MKL	Benign	0.013	N
LIST_S2	Benign	0.48	.;T
M_CAP	Benign	0.0018	T
MetaRNN	Benign	0.040	T;T
MetaSVM	Benign	-0.93	T
MutationAssessor	Benign	-0.14	N;N
PrimateAI	Benign	0.43	T
PROVEAN	Benign	0.29	N;N
REVEL	Benign	0.11
Sift	Benign	0.51	T;T
Sift4G	Benign	0.12	T;T
Polyphen		0.0	B;B
Vest4		0.10
MutPred		0.26		Loss of phosphorylation at T220 (P = 0.1329);Loss of phosphorylation at T220 (P = 0.1329);
MVP		0.030
MPC		0.43
ClinPred		0.046	T
GERP RS		2.8
Varity_R		0.030
gMVP		0.045

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: rs1839201894; hg19: chr10-44139661;