NM_006973.3:c.221A>C

Variant names:

• chr10-43644651-T-G
• rs775158350
• NM_006973.3:c.221A>C

Variant summary

Our verdict is Uncertain significance. The variant received 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. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. Q74R) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: ZNF32 NM_006973.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.12
• Publications: 0 publications found

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-AS2 (HGNC:23593): (ZNF32 antisense RNA 2)

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

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

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=0.22161943).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006973.3. 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
	ZNF32	NM_006973.3	MANE Select	c.221A>C	p.Gln74Pro	missense	Exon 3 of 3	NP_008904.1	P17041
	ZNF32	NM_001324164.2		c.233A>C	p.Gln78Pro	missense	Exon 3 of 3	NP_001311093.1
	ZNF32	NM_001324165.2		c.233A>C	p.Gln78Pro	missense	Exon 3 of 3	NP_001311094.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZNF32	ENST00000374433.7	TSL:1 MANE Select	c.221A>C	p.Gln74Pro	missense	Exon 3 of 3	ENSP00000363556.2	P17041
	ZNF32-AS2	ENST00000458063.1	TSL:1	n.162+15673T>G		intron	N/A
	ZNF32	ENST00000395797.1	TSL:2	c.221A>C	p.Gln74Pro	missense	Exon 3 of 3	ENSP00000379143.1	P17041

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

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86256

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53420

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5766

European-Non Finnish (NFE) AF: 8.99e-7 AC: 1 AN: 1112010

Other (OTH) AF: 0.00 AC: 0 AN: 60396

GnomAD4 genome Cov.: 33

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	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
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
MetaSVM	Benign	-0.97	T
MutationAssessor	Benign	0.0	N
PhyloP100		5.1
PrimateAI	Benign	0.47	T
PROVEAN	Benign	-0.51	N
REVEL	Benign	0.091
Sift	Uncertain	0.0010	D
Sift4G	Uncertain	0.045	D
Polyphen		0.90	P
Vest4		0.50
MutPred		0.31		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
Mutation Taster		=84/16	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: rs775158350; hg19: chr10-44140099;