6-26638178-A-C

Variant names:

• chr6-26638178-A-C
• NM_024639.5:c.376T>G

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_024639.5(ZNF322):​c.376T>G​(p.Phe126Val) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 24)
• Consequence: ZNF322 NM_024639.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.72
• 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: 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=0.102411).

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.376T>G	p.Phe126Val	missense	Exon 4 of 4	NP_078915.2
	ZNF322	NM_001242797.2		c.376T>G	p.Phe126Val	missense	Exon 5 of 5	NP_001229726.1	Q6U7Q0
	ZNF322	NM_001242798.2		c.376T>G	p.Phe126Val	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.376T>G	p.Phe126Val	missense	Exon 4 of 4	ENSP00000418897.1	Q6U7Q0
	ZNF322	ENST00000456172.5	TSL:3	c.376T>G	p.Phe126Val	missense	Exon 3 of 3	ENSP00000478899.1	Q6U7Q0
	ZNF322	ENST00000471278.5	TSL:5	c.376T>G	p.Phe126Val	missense	Exon 4 of 4	ENSP00000419728.1	Q6U7Q0

Frequencies

GnomAD3 genomes Cov.: 24

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 24

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	0.14
BayesDel_addAF	Benign	-0.040	T
BayesDel_noAF	Benign	-0.30
CADD	Benign	23
DANN	Uncertain	0.98
DEOGEN2	Benign	0.0013	T
Eigen	Benign	-0.16
Eigen_PC	Benign	0.069
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Uncertain	0.86	D
M_CAP	Benign	0.0020	T
MetaRNN	Benign	0.10	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-0.78	N
PhyloP100		3.7
PrimateAI	Uncertain	0.72	T
PROVEAN	Benign	1.7	N
REVEL	Benign	0.18
Sift	Uncertain	0.014	D
Sift4G	Uncertain	0.0030	D
Polyphen		0.048	B
Vest4		0.29
MutPred		0.56		Loss of helix (P = 0.1299)
MVP		0.014
ClinPred		0.74	D
GERP RS		5.2
Varity_R		0.081
gMVP		0.082
Mutation Taster		=78/22	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

hg19: chr6-26638406;