NM_006973.3:c.346G>A

Variant names:

• chr10-43644526-C-T
• rs899135140
• NM_006973.3:c.346G>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_006973.3(ZNF32):​c.346G>A​(p.Ala116Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000124 in 1,613,946 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000046 (0 hom., cov: 33)
  • Exomes 𝑓: 0.0000089 (0 hom.)
• Consequence: ZNF32 NM_006973.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.740
• 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.06261444).

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.346G>A	p.Ala116Thr	missense	Exon 3 of 3	NP_008904.1	P17041
	ZNF32	NM_001324164.2		c.358G>A	p.Ala120Thr	missense	Exon 3 of 3	NP_001311093.1
	ZNF32	NM_001324165.2		c.358G>A	p.Ala120Thr	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.346G>A	p.Ala116Thr	missense	Exon 3 of 3	ENSP00000363556.2	P17041
	ZNF32-AS2	ENST00000458063.1	TSL:1	n.162+15548C>T		intron	N/A
	ZNF32	ENST00000395797.1	TSL:2	c.346G>A	p.Ala116Thr	missense	Exon 3 of 3	ENSP00000379143.1	P17041

Frequencies

GnomAD3 genomes AF: 0.0000460 AC: 7 AN: 152140 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.000145

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000159 AC: 4 AN: 251272 AF XY: 0.0000221

Gnomad AFR exome AF: 0.000185

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000880

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000889 AC: 13 AN: 1461806 Hom.: 0 Cov.: 31 AF XY: 0.0000138 AC XY: 10 AN XY: 727204

African (AFR) AF: 0.0000896 AC: 3 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44718

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26124

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

South Asian (SAS) AF: 0.00 AC: 0 AN: 86250

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53418

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.00000630 AC: 7 AN: 1111956

Other (OTH) AF: 0.0000497 AC: 3 AN: 60392

GnomAD4 genome AF: 0.0000460 AC: 7 AN: 152140 Hom.: 0 Cov.: 33 AF XY: 0.0000269 AC XY: 2 AN XY: 74326

African (AFR) AF: 0.000145 AC: 6 AN: 41414

American (AMR) AF: 0.00 AC: 0 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5188

South Asian (SAS) AF: 0.00 AC: 0 AN: 4824

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10610

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 68034

Other (OTH) AF: 0.00 AC: 0 AN: 2092

Alfa AF: 0.0000386 Hom.: 0

Bravo AF: 0.0000529

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	Uncertain	0.42
BayesDel_addAF	Benign	-0.38	T
BayesDel_noAF	Benign	-0.55
CADD	Benign	19
DANN	Uncertain	0.99
DEOGEN2	Benign	0.020	T
Eigen	Benign	-0.39
Eigen_PC	Benign	-0.22
FATHMM_MKL	Benign	0.0035	N
LIST_S2	Benign	0.58	T
M_CAP	Benign	0.0021	T
MetaRNN	Benign	0.063	T
MetaSVM	Benign	-0.94	T
MutationAssessor	Benign	-1.6	N
PhyloP100		-0.74
PrimateAI	Uncertain	0.66	T
PROVEAN	Benign	-0.16	N
REVEL	Benign	0.078
Sift	Benign	0.10	T
Sift4G	Benign	0.097	T
Polyphen		0.35	B
Vest4		0.061
MutPred		0.34		Gain of disorder (P = 0.0539)
MVP		0.014
MPC		0.47
ClinPred		0.18	T
GERP RS		4.5
Varity_R		0.042
gMVP		0.11
Mutation Taster		=74/26	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: rs899135140; hg19: chr10-44139974;