NM_001085457.2:c.445A>G

Variant names:

• chr9-41174338-T-C
• rs776177539
• NM_001085457.2:c.445A>G

Variant summary

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

The NM_001085457.2(ZNG1F):​c.445A>G​(p.Met149Val) variant causes a missense change. The variant allele was found at a frequency of 0.000147 in 149,592 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00015 (0 hom., cov: 26)
  • Exomes 𝑓: 0.00012 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: ZNG1F NM_001085457.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.08
• 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.445A>G	p.Met149Val	missense	Exon 5 of 15	NP_001078926.1	Q4V339
	ZNG1F	NM_001439294.1		c.431-1589A>G		intron	N/A	NP_001426223.1
	ZNG1F	NM_001386876.1		c.431-1589A>G		intron	N/A	NP_001373805.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZNG1F	ENST00000377391.8	TSL:1 MANE Select	c.445A>G	p.Met149Val	missense	Exon 5 of 15	ENSP00000366608.4	Q4V339
	ZNG1F	ENST00000456520.5	TSL:1	c.445A>G	p.Met149Val	missense	Exon 5 of 14	ENSP00000401079.2	H0Y5V3
	ZNG1F	ENST00000382436.7	TSL:1	n.313A>G		non_coding_transcript_exon	Exon 5 of 16	ENSP00000484049.1	A0A087X1C0

Frequencies

GnomAD3 genomes AF: 0.000147 AC: 22 AN: 149504 Hom.: 0 Cov.: 26

Gnomad AFR AF: 0.0000247

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000269

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.0000994

Gnomad MID AF: 0.00323

Gnomad NFE AF: 0.000222

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000436 AC: 6 AN: 137716 AF XY: 0.0000653

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000187

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.0000843

Gnomad NFE exome AF: 0.0000327

Gnomad OTH exome AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.000117 AC: 169 AN: 1444980 Hom.: 0 Cov.: 36 AF XY: 0.000124 AC XY: 89 AN XY: 718410

⚠️ 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: 32674

American (AMR) AF: 0.000351 AC: 15 AN: 42756

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25556

East Asian (EAS) AF: 0.0000511 AC: 2 AN: 39108

South Asian (SAS) AF: 0.0000119 AC: 1 AN: 83850

European-Finnish (FIN) AF: 0.0000379 AC: 2 AN: 52766

Middle Eastern (MID) AF: 0.000987 AC: 4 AN: 4052

European-Non Finnish (NFE) AF: 0.000129 AC: 142 AN: 1104764

Other (OTH) AF: 0.0000505 AC: 3 AN: 59454

⚠️ 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 AF: 0.000147 AC: 22 AN: 149592 Hom.: 0 Cov.: 26 AF XY: 0.000123 AC XY: 9 AN XY: 72920

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

African (AFR) AF: 0.0000246 AC: 1 AN: 40598

American (AMR) AF: 0.000269 AC: 4 AN: 14892

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3458

East Asian (EAS) AF: 0.00 AC: 0 AN: 5096

South Asian (SAS) AF: 0.00 AC: 0 AN: 4710

European-Finnish (FIN) AF: 0.0000994 AC: 1 AN: 10060

Middle Eastern (MID) AF: 0.00350 AC: 1 AN: 286

European-Non Finnish (NFE) AF: 0.000222 AC: 15 AN: 67494

Other (OTH) AF: 0.00 AC: 0 AN: 2086

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

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	0.083
BayesDel_noAF	Benign	-0.32
CADD	Benign	22
DANN	Benign	0.66
DEOGEN2	Benign	0.015	T
LIST_S2	Uncertain	0.94	D
MetaRNN	Uncertain	0.60	D
PhyloP100		7.1
PROVEAN	Benign	0.13	N
Sift	Benign	1.0	T
Sift4G	Benign	0.27	T
Vest4		0.73
gMVP		0.48

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.14		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: rs776177539; hg19: chr9-70871851;