NM_001085457.2:c.944G>A

Variant names:

• chr9-41133512-C-T
• rs1312833947
• NM_001085457.2:c.944G>A

Variant summary

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

The NM_001085457.2(ZNG1F):​c.944G>A​(p.Arg315Lys) variant causes a missense change. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000053 (0 hom., cov: 11)
  • Exomes 𝑓: 0.000039 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: ZNG1F NM_001085457.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.85
• Publications: 0 publications found

Genes affected

ZNG1F (HGNC:31978): (Zn regulated GTPase metalloprotein activator 1F) Predicted to enable ATP binding activity. Predicted to be active in cytoplasm. [provided by Alliance of Genome Resources, Apr 2022]

FRG1HP (HGNC:51767): (FSHD region gene 1 family member H, pseudogene)

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001085457.2. 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
	ZNG1F	NM_001085457.2	MANE Select	c.944G>A	p.Arg315Lys	missense	Exon 13 of 15	NP_001078926.1	Q4V339
	ZNG1F	NM_001439294.1		c.929G>A	p.Arg310Lys	missense	Exon 13 of 15	NP_001426223.1
	ZNG1F	NM_001386876.1		c.884G>A	p.Arg295Lys	missense	Exon 12 of 14	NP_001373805.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZNG1F	ENST00000377391.8	TSL:1 MANE Select	c.944G>A	p.Arg315Lys	missense	Exon 13 of 15	ENSP00000366608.4	Q4V339
	ZNG1F	ENST00000456520.5	TSL:1	c.887G>A	p.Arg296Lys	missense	Exon 12 of 14	ENSP00000401079.2	H0Y5V3
	ZNG1F	ENST00000382436.7	TSL:1	n.*489G>A		non_coding_transcript_exon	Exon 14 of 16	ENSP00000484049.1	A0A087X1C0

Frequencies

GnomAD3 genomes AF: 0.0000531 AC: 5 AN: 94106 Hom.: 0 Cov.: 11

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000406

Gnomad ASJ AF: 0.000733

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000991 AC: 2 AN: 20174 AF XY: 0.000187

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000519

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.0000390 AC: 50 AN: 1281098 Hom.: 0 Cov.: 20 AF XY: 0.0000466 AC XY: 30 AN XY: 643666

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

African (AFR) AF: 0.00 AC: 0 AN: 30184

American (AMR) AF: 0.000232 AC: 10 AN: 43058

Ashkenazi Jewish (ASJ) AF: 0.00116 AC: 29 AN: 25050

East Asian (EAS) AF: 0.00 AC: 0 AN: 37886

South Asian (SAS) AF: 0.00 AC: 0 AN: 80928

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 38572

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3838

European-Non Finnish (NFE) AF: 0.00000724 AC: 7 AN: 967212

Other (OTH) AF: 0.0000736 AC: 4 AN: 54370

⚠️ 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 Data not reliable, filtered out with message: AS_VQSR AF: 0.0000531 AC: 5 AN: 94190 Hom.: 0 Cov.: 11 AF XY: 0.0000927 AC XY: 4 AN XY: 43128

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

African (AFR) AF: 0.00 AC: 0 AN: 25016

American (AMR) AF: 0.000405 AC: 3 AN: 7410

Ashkenazi Jewish (ASJ) AF: 0.000733 AC: 2 AN: 2728

East Asian (EAS) AF: 0.00 AC: 0 AN: 2988

South Asian (SAS) AF: 0.00 AC: 0 AN: 2228

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 3744

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 258

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 47894

Other (OTH) AF: 0.00 AC: 0 AN: 1206

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0.000852049), which strongly suggests a high chance of mosaicism in these individuals.

Alfa AF: 0.0000843 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	Pathogenic	0.79
BayesDel_noAF	Pathogenic	0.28
CADD	Pathogenic	28
DANN	Uncertain	0.99
DEOGEN2	Benign	0.25	T
LIST_S2	Uncertain	0.95	D
MetaRNN	Uncertain	0.68	D
PhyloP100		6.9
Sift4G	Pathogenic	0.0	D
Vest4		0.76
gMVP		0.83

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: rs1312833947; hg19: chr9-70912726;