chr6-26637643-C-T

Variant names:

• chr6-26637643-C-T
• rs1388989086
• NM_024639.5:c.911G>A

Variant summary

Our verdict is Likely benign. Variant got -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. 14/20 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

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 -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.06061867).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZNF322	NM_024639.5	c.911G>A	p.Cys304Tyr	missense_variant	Exon 4 of 4	ENST00000415922.7	NP_078915.2
ZNF322	NM_001242797.2	c.911G>A	p.Cys304Tyr	missense_variant	Exon 5 of 5		NP_001229726.1
ZNF322	NM_001242798.2	c.911G>A	p.Cys304Tyr	missense_variant	Exon 3 of 3		NP_001229727.1
ZNF322	NM_001242799.2	c.911G>A	p.Cys304Tyr	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.911G>A	p.Cys304Tyr	missense_variant	Exon 4 of 4	1	NM_024639.5	ENSP00000418897.1

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

Gnomad4 AFR exome AF: 0.0000333

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 14

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

May 27, 2022

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.911G>A (p.C304Y) alteration is located in exon 5 (coding exon 1) of the ZNF322 gene. This alteration results from a G to A substitution at nucleotide position 911, causing the cysteine (C) at amino acid position 304 to be replaced by a tyrosine (Y). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

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;T;T;T;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;T;T;T;T
MetaSVM	Benign	-0.97	T
MutationAssessor	Benign	-0.090	N;N;N;N;N
PrimateAI	Uncertain	0.75	T
PROVEAN	Benign	0.95	N;.;.;.;N
REVEL	Benign	0.15
Sift	Benign	1.0	T;.;.;.;T
Sift4G	Benign	0.55	T;T;T;T;T
Polyphen		0.14	B;B;B;B;B
Vest4		0.24
MutPred		0.27		Loss of stability (P = 0.0672);Loss of stability (P = 0.0672);Loss of stability (P = 0.0672);Loss of stability (P = 0.0672);Loss of stability (P = 0.0672);
MVP		0.21
ClinPred		0.45	T
GERP RS		4.6
Varity_R		0.15
gMVP		0.040

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: rs1388989086; hg19: chr6-26637871;