1-90007373-A-G

Variant names:

• chr1-90007373-A-G
• rs1447698642
• NM_182976.4:c.238A>G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_182976.4(ZNF326):​c.238A>G​(p.Arg80Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: ZNF326 NM_182976.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.39

Genes affected

ZNF326 (HGNC:14104): (zinc finger protein 326) Enables RNA polymerase II complex binding activity. Involved in regulation of DNA-templated transcription, elongation and regulation of RNA splicing. Located in nucleoplasm. Part of DBIRD complex. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.14845994).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZNF326	NM_182976.4	c.238A>G	p.Arg80Gly	missense_variant	Exon 5 of 12	ENST00000340281.9	NP_892021.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZNF326	ENST00000340281.9	c.238A>G	p.Arg80Gly	missense_variant	Exon 5 of 12	1	NM_182976.4	ENSP00000340796.4
ZNF326	ENST00000370447.3	c.210-239A>G		intron_variant	Intron 4 of 11	1		ENSP00000359476.2
ZNF326	ENST00000394583.7	n.151+2281A>G		intron_variant	Intron 3 of 9	1		ENSP00000378084.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1459832 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 726148

Gnomad4 AFR exome AF: 0.00

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.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Mar 30, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.238A>G (p.R80G) alteration is located in exon 5 (coding exon 5) of the ZNF326 gene. This alteration results from a A to G substitution at nucleotide position 238, causing the arginine (R) at amino acid position 80 to be replaced by a glycine (G). 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	0.13
BayesDel_addAF	Benign	-0.11	T
BayesDel_noAF	Benign	-0.39
CADD	Uncertain	25
DANN	Benign	0.97
DEOGEN2	Benign	0.28	T
Eigen	Benign	-0.47
Eigen_PC	Benign	-0.27
FATHMM_MKL	Benign	0.71	D
LIST_S2	Benign	0.84	T
M_CAP	Benign	0.011	T
MetaRNN	Benign	0.15	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.2	L
PrimateAI	Uncertain	0.53	T
PROVEAN	Uncertain	-3.3	D
REVEL	Benign	0.11
Sift	Benign	0.20	T
Sift4G	Benign	0.43	T
Polyphen		0.0	B
Vest4		0.38
MutPred		0.32		Gain of glycosylation at S79 (P = 0.0647);
MVP		0.043
MPC		0.37
ClinPred		0.63	D
GERP RS		3.4
Varity_R		0.16
gMVP		0.43

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: rs1447698642; hg19: chr1-90472932;