6-26638033-C-T

Variant names:

• chr6-26638033-C-T
• rs781862075
• NM_024639.5:c.521G>A

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_024639.5(ZNF322):​c.521G>A​(p.Arg174Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000016 (0 hom., cov: 17)
  • Exomes 𝑓: 0.000076 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: ZNF322 NM_024639.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.349
• Publications: 0 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 -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.015612662).

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.521G>A	p.Arg174Gln	missense	Exon 4 of 4	NP_078915.2
	ZNF322	NM_001242797.2		c.521G>A	p.Arg174Gln	missense	Exon 5 of 5	NP_001229726.1	Q6U7Q0
	ZNF322	NM_001242798.2		c.521G>A	p.Arg174Gln	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.521G>A	p.Arg174Gln	missense	Exon 4 of 4	ENSP00000418897.1	Q6U7Q0
	ZNF322	ENST00000456172.5	TSL:3	c.521G>A	p.Arg174Gln	missense	Exon 3 of 3	ENSP00000478899.1	Q6U7Q0
	ZNF322	ENST00000471278.5	TSL:5	c.521G>A	p.Arg174Gln	missense	Exon 4 of 4	ENSP00000419728.1	Q6U7Q0

Frequencies

GnomAD3 genomes AF: 0.0000159 AC: 2 AN: 125530 Hom.: 0 Cov.: 17

Gnomad AFR AF: 0.00

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: 0.0000339

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000956 AC: 13 AN: 135982 AF XY: 0.000122

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000161

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000151

Gnomad OTH exome AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.0000758 AC: 79 AN: 1041652 Hom.: 0 Cov.: 13 AF XY: 0.0000789 AC XY: 42 AN XY: 532450

African (AFR) AF: 0.0000391 AC: 1 AN: 25594

American (AMR) AF: 0.000124 AC: 5 AN: 40294

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 22654

East Asian (EAS) AF: 0.00 AC: 0 AN: 37380

South Asian (SAS) AF: 0.00 AC: 0 AN: 75206

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 51234

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4510

European-Non Finnish (NFE) AF: 0.0000989 AC: 73 AN: 738444

Other (OTH) AF: 0.00 AC: 0 AN: 46336

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.0000159 AC: 2 AN: 125530 Hom.: 0 Cov.: 17 AF XY: 0.0000168 AC XY: 1 AN XY: 59542

African (AFR) AF: 0.00 AC: 0 AN: 33790

American (AMR) AF: 0.00 AC: 0 AN: 11728

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3060

East Asian (EAS) AF: 0.00 AC: 0 AN: 4434

South Asian (SAS) AF: 0.00 AC: 0 AN: 3374

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 7548

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000339 AC: 2 AN: 58986

Other (OTH) AF: 0.00 AC: 0 AN: 1498

Alfa AF: 0.000169 Hom.: 0

ExAC AF: 0.0000766 AC: 9

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	0.091
BayesDel_addAF	Benign	-0.47	T
BayesDel_noAF	Benign	-0.65
CADD	Benign	18
DANN	Benign	0.85
DEOGEN2	Benign	0.0011	T
Eigen	Benign	-0.79
Eigen_PC	Benign	-0.60
FATHMM_MKL	Benign	0.076	N
LIST_S2	Benign	0.56	T
M_CAP	Benign	0.0018	T
MetaRNN	Benign	0.016	T
MetaSVM	Benign	-0.91	T
MutationAssessor	Benign	-0.66	N
PhyloP100		0.35
PrimateAI	Uncertain	0.65	T
PROVEAN	Benign	2.3	N
REVEL	Benign	0.097
Sift	Benign	1.0	T
Sift4G	Benign	1.0	T
Polyphen		0.0	B
Vest4		0.12
MutPred		0.38		Loss of MoRF binding (P = 0.0461)
MVP		0.014
ClinPred		0.027	T
GERP RS		3.1
Varity_R		0.043
gMVP		0.12
Mutation Taster		=96/4	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: rs781862075; hg19: chr6-26638261;