10-43644651-T-G

Variant names:

• chr10-43644651-T-G
• NM_006973.3:c.221A>C

Variant summary

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

The NM_006973.3(ZNF32):​c.221A>C​(p.Gln74Pro) variant causes a missense change. The variant allele was found at a frequency of 0.000000684 in 1,461,888 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 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: 6.8e-7 (0 hom.)
• Consequence: ZNF32 NM_006973.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.12

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 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=0.22161943).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZNF32	NM_006973.3	c.221A>C	p.Gln74Pro	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.221A>C	p.Gln74Pro	missense_variant	Exon 3 of 3	1	NM_006973.3	ENSP00000363556.2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461888 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 727244

Gnomad4 AFR exome AF: 0.00

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: 8.99e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.084
BayesDel_addAF	Benign	-0.073	T
BayesDel_noAF	Benign	-0.34
CADD	Benign	23
DANN	Uncertain	0.99
DEOGEN2	Benign	0.042	T;T
Eigen	Benign	0.12
Eigen_PC	Benign	0.18
FATHMM_MKL	Benign	0.41	N
LIST_S2	Benign	0.062	.;T
M_CAP	Benign	0.0062	T
MetaRNN	Benign	0.22	T;T
MetaSVM	Benign	-0.97	T
MutationAssessor	Benign	0.0	N;N
PrimateAI	Benign	0.47	T
PROVEAN	Benign	-0.51	N;N
REVEL	Benign	0.091
Sift	Uncertain	0.0010	D;D
Sift4G	Uncertain	0.045	D;D
Polyphen		0.90	P;P
Vest4		0.50
MutPred		0.31		Gain of glycosylation at S69 (P = 0.1507);Gain of glycosylation at S69 (P = 0.1507);
MVP		0.014
MPC		1.2
ClinPred		0.62	D
GERP RS		4.5
Varity_R		0.11
gMVP		0.46

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: chr10-44140099;