6-26638486-C-T

Variant names:

• chr6-26638486-C-T
• rs536011469
• NM_024639.5:c.68G>A

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_Strong BP6_Moderate

The NM_024639.5(ZNF322):​c.68G>A​(p.Arg23Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000197 in 152,082 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.00020 (0 hom., cov: 29)
  • Exomes 𝑓: 0.00038 (1 hom.)
  • Failed GnomAD Quality Control
• Consequence: ZNF322 NM_024639.5 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.466

Genes affected

ZNF322 (HGNC:23640): (zinc finger protein 322) ZNF322A is a member of the zinc-finger transcription factor family and may regulate transcriptional activation in MAPK (see MAPK1; MIM 176948) signaling pathways (Li et al., 2004 [PubMed 15555580]).[supplied by OMIM, Mar 2008]

ACMG classification

Verdict is Likely_benign. Variant got -6 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.007117659).
• BP6: Variant 6-26638486-C-T is Benign according to our data. Variant chr6-26638486-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 2264248.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZNF322	NM_024639.5	c.68G>A	p.Arg23Gln	missense_variant	Exon 4 of 4	ENST00000415922.7	NP_078915.2
ZNF322	NM_001242797.2	c.68G>A	p.Arg23Gln	missense_variant	Exon 5 of 5		NP_001229726.1
ZNF322	NM_001242798.2	c.68G>A	p.Arg23Gln	missense_variant	Exon 3 of 3		NP_001229727.1
ZNF322	NM_001242799.2	c.68G>A	p.Arg23Gln	missense_variant	Exon 3 of 3		NP_001229728.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZNF322	ENST00000415922.7	c.68G>A	p.Arg23Gln	missense_variant	Exon 4 of 4	1	NM_024639.5	ENSP00000418897.1

Frequencies

GnomAD3 genomes AF: 0.000197 AC: 30 AN: 152082 Hom.: 0 Cov.: 29

Gnomad AFR AF: 0.0000241

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000131

Gnomad ASJ AF: 0.00173

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000294

Gnomad OTH AF: 0.000479

GnomAD3 exomes AF: 0.000288 AC: 68 AN: 236126 Hom.: 0 AF XY: 0.000281 AC XY: 36 AN XY: 128224

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000283

Gnomad ASJ exome AF: 0.00179

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000107

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000362

Gnomad OTH exome AF: 0.000178

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.000383 AC: 559 AN: 1459594 Hom.: 1 Cov.: 30 AF XY: 0.000372 AC XY: 270 AN XY: 726194

Gnomad4 AFR exome AF: 0.0000599

Gnomad4 AMR exome AF: 0.000382

Gnomad4 ASJ exome AF: 0.00180

Gnomad4 EAS exome AF: 0.0000252

Gnomad4 SAS exome AF: 0.0000465

Gnomad4 FIN exome AF: 0.0000375

Gnomad4 NFE exome AF: 0.000424

Gnomad4 OTH exome AF: 0.000249

GnomAD4 genome AF: 0.000197 AC: 30 AN: 152082 Hom.: 0 Cov.: 29 AF XY: 0.000202 AC XY: 15 AN XY: 74296

Gnomad4 AFR AF: 0.0000241

Gnomad4 AMR AF: 0.000131

Gnomad4 ASJ AF: 0.00173

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000294

Gnomad4 OTH AF: 0.000479

Alfa AF: 0.000287 Hom.: 0

Bravo AF: 0.000181

ExAC AF: 0.000297 AC: 36

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Jul 26, 2021

Ambry Genetics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.087
BayesDel_addAF	Benign	-0.57	T
BayesDel_noAF	Benign	-0.75
CADD	Benign	4.3
DANN	Benign	0.68
DEOGEN2	Benign	0.0031	T;T;T;T;T;.
Eigen	Benign	-1.3
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.0016	N
LIST_S2	Benign	0.31	.;.;.;T;.;T
M_CAP	Benign	0.0041	T
MetaRNN	Benign	0.0071	T;T;T;T;T;T
MetaSVM	Benign	-0.91	T
MutationAssessor	Benign	-0.34	N;N;N;N;N;.
PrimateAI	Benign	0.23	T
PROVEAN	Benign	0.61	N;.;.;.;N;N
REVEL	Benign	0.038
Sift	Benign	1.0	T;.;.;.;T;T
Sift4G	Benign	0.32	T;T;T;T;T;.
Polyphen		0.0	B;B;B;B;B;.
Vest4		0.048
MVP		0.014
ClinPred		0.0028	T
GERP RS		0.84
Varity_R		0.026
gMVP		0.023

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: rs536011469; hg19: chr6-26638714;