chr6-26637643-C-T

Variant names:

• chr6-26637643-C-T
• rs1388989086
• NM_024639.5:c.911G>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.911G>A​(p.Cys304Tyr) 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: not found (cov: 14)
  • Exomes 𝑓: 8.8e-7 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: ZNF322 NM_024639.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.0150
• 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=0.06061867).

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.911G>A	p.Cys304Tyr	missense	Exon 4 of 4	NP_078915.2
	ZNF322	NM_001242797.2		c.911G>A	p.Cys304Tyr	missense	Exon 5 of 5	NP_001229726.1	Q6U7Q0
	ZNF322	NM_001242798.2		c.911G>A	p.Cys304Tyr	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.911G>A	p.Cys304Tyr	missense	Exon 4 of 4	ENSP00000418897.1	Q6U7Q0
	ZNF322	ENST00000456172.5	TSL:3	c.911G>A	p.Cys304Tyr	missense	Exon 3 of 3	ENSP00000478899.1	Q6U7Q0
	ZNF322	ENST00000471278.5	TSL:5	c.911G>A	p.Cys304Tyr	missense	Exon 4 of 4	ENSP00000419728.1	Q6U7Q0

Frequencies

GnomAD3 genomes Cov.: 14

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 8.79e-7 AC: 1 AN: 1137210 Hom.: 0 Cov.: 16 AF XY: 0.00 AC XY: 0 AN XY: 574392

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.0000333 AC: 1 AN: 30022

American (AMR) AF: 0.00 AC: 0 AN: 42024

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 22630

East Asian (EAS) AF: 0.00 AC: 0 AN: 38476

South Asian (SAS) AF: 0.00 AC: 0 AN: 77268

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52086

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4252

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 820838

Other (OTH) AF: 0.00 AC: 0 AN: 49614

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 14

Alfa AF: 0.00 Hom.: 0

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	0.24
BayesDel_addAF	Benign	-0.086	T
BayesDel_noAF	Benign	-0.36
CADD	Benign	16
DANN	Benign	0.85
DEOGEN2	Benign	0.00075	T
Eigen	Benign	-0.43
Eigen_PC	Benign	-0.29
FATHMM_MKL	Benign	0.085	N
LIST_S2	Benign	0.61	T
M_CAP	Benign	0.0054	T
MetaRNN	Benign	0.061	T
MetaSVM	Benign	-0.97	T
MutationAssessor	Benign	-0.090	N
PhyloP100		-0.015
PrimateAI	Uncertain	0.75	T
PROVEAN	Benign	0.95	N
REVEL	Benign	0.15
Sift	Benign	1.0	T
Sift4G	Benign	0.55	T
Polyphen		0.14	B
Vest4		0.24
MutPred		0.27		Loss of stability (P = 0.0672)
MVP		0.21
ClinPred		0.45	T
GERP RS		4.6
Varity_R		0.15
gMVP		0.040
Mutation Taster		=81/19	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: rs1388989086; hg19: chr6-26637871;