chr6-26638486-C-T

Variant names:

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

Variant summary

Our verdict is Likely benign. The variant received -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. 16/22 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
• Publications: 1 publications found

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

Our verdict: Likely_benign. The variant received -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 VariationId is 2264248.Status of the report is criteria_provided_single_submitter, 1 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_024639.5. 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
	ZNF322	NM_024639.5	MANE Select	c.68G>A	p.Arg23Gln	missense	Exon 4 of 4	NP_078915.2
	ZNF322	NM_001242797.2		c.68G>A	p.Arg23Gln	missense	Exon 5 of 5	NP_001229726.1	Q6U7Q0
	ZNF322	NM_001242798.2		c.68G>A	p.Arg23Gln	missense	Exon 3 of 3	NP_001229727.1	Q6U7Q0

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZNF322	ENST00000415922.7	TSL:1 MANE Select	c.68G>A	p.Arg23Gln	missense	Exon 4 of 4	ENSP00000418897.1	Q6U7Q0
	ZNF322	ENST00000456172.5	TSL:3	c.68G>A	p.Arg23Gln	missense	Exon 3 of 3	ENSP00000478899.1	Q6U7Q0
	ZNF322	ENST00000471278.5	TSL:5	c.68G>A	p.Arg23Gln	missense	Exon 4 of 4	ENSP00000419728.1	Q6U7Q0

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

GnomAD2 exomes AF: 0.000288 AC: 68 AN: 236126 AF XY: 0.000281

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 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

African (AFR) AF: 0.0000599 AC: 2 AN: 33402

American (AMR) AF: 0.000382 AC: 17 AN: 44530

Ashkenazi Jewish (ASJ) AF: 0.00180 AC: 47 AN: 26040

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39676

South Asian (SAS) AF: 0.0000465 AC: 4 AN: 85986

European-Finnish (FIN) AF: 0.0000375 AC: 2 AN: 53396

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5750

European-Non Finnish (NFE) AF: 0.000424 AC: 471 AN: 1110536

Other (OTH) AF: 0.000249 AC: 15 AN: 60278

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

African (AFR) AF: 0.0000241 AC: 1 AN: 41432

American (AMR) AF: 0.000131 AC: 2 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.00173 AC: 6 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5196

South Asian (SAS) AF: 0.00 AC: 0 AN: 4822

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10588

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

European-Non Finnish (NFE) AF: 0.000294 AC: 20 AN: 68000

Other (OTH) AF: 0.000479 AC: 1 AN: 2088

Alfa AF: 0.000287 Hom.: 0

Bravo AF: 0.000181

ExAC AF: 0.000297 AC: 36

ClinVar

ClinVar submissions

Significance: Likely benign

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	0.087
BayesDel_addAF	Benign	-0.57	T
BayesDel_noAF	Benign	-0.75
CADD	Benign	4.3
DANN	Benign	0.68
DEOGEN2	Benign	0.0031	T
Eigen	Benign	-1.3
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.0016	N
LIST_S2	Benign	0.31	T
M_CAP	Benign	0.0041	T
MetaRNN	Benign	0.0071	T
MetaSVM	Benign	-0.91	T
MutationAssessor	Benign	-0.34	N
PhyloP100		0.47
PrimateAI	Benign	0.23	T
PROVEAN	Benign	0.61	N
REVEL	Benign	0.038
Sift	Benign	1.0	T
Sift4G	Benign	0.32	T
Polyphen		0.0	B
Vest4		0.048
MVP		0.014
ClinPred		0.0028	T
GERP RS		0.84
Varity_R		0.026
gMVP		0.023
Mutation Taster		=98/2	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: rs536011469; hg19: chr6-26638714;