rs373196176

Variant names:

• chr9-41133718-C-T
• rs373196176
• NM_001085457.2:c.841G>A

Your query was ambiguous. Multiple possible variants found:

• chr9-41133718-C-T
• chr9-41133718-C-G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_001085457.2(ZNG1F):​c.841G>A​(p.Val281Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000258 in 151,042 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 8/10 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00026 (0 hom., cov: 28)
  • Exomes 𝑓: 0.000066 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: ZNG1F NM_001085457.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.10
• 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: Likely_benign. The variant received -2 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.09296885).

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.841G>A	p.Val281Ile	missense	Exon 12 of 15	NP_001078926.1	Q4V339
	ZNG1F	NM_001439294.1		c.826G>A	p.Val276Ile	missense	Exon 12 of 15	NP_001426223.1
	ZNG1F	NM_001386876.1		c.781G>A	p.Val261Ile	missense	Exon 11 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.841G>A	p.Val281Ile	missense	Exon 12 of 15	ENSP00000366608.4	Q4V339
	ZNG1F	ENST00000456520.5	TSL:1	c.784G>A	p.Val262Ile	missense	Exon 11 of 14	ENSP00000401079.2	H0Y5V3
	ZNG1F	ENST00000382436.7	TSL:1	n.*386G>A		non_coding_transcript_exon	Exon 13 of 16	ENSP00000484049.1	A0A087X1C0

Frequencies

GnomAD3 genomes AF: 0.000258 AC: 39 AN: 150920 Hom.: 0 Cov.: 28

Gnomad AFR AF: 0.000707

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000664

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000984

Gnomad SAS AF: 0.000211

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000443

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000214 AC: 41 AN: 191378 AF XY: 0.000169

Gnomad AFR exome AF: 0.00101

Gnomad AMR exome AF: 0.000126

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00112

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000317

Gnomad OTH exome AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.0000665 AC: 96 AN: 1444080 Hom.: 0 Cov.: 41 AF XY: 0.0000807 AC XY: 58 AN XY: 718800

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

African (AFR) AF: 0.000330 AC: 11 AN: 33310

American (AMR) AF: 0.00 AC: 0 AN: 44592

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26114

East Asian (EAS) AF: 0.000581 AC: 23 AN: 39558

South Asian (SAS) AF: 0.000290 AC: 25 AN: 86098

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 39132

Middle Eastern (MID) AF: 0.000242 AC: 1 AN: 4130

European-Non Finnish (NFE) AF: 0.0000279 AC: 31 AN: 1111104

Other (OTH) AF: 0.0000833 AC: 5 AN: 60042

⚠️ 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: 0.000258 AC: 39 AN: 151042 Hom.: 0 Cov.: 28 AF XY: 0.000203 AC XY: 15 AN XY: 73790

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

African (AFR) AF: 0.000705 AC: 29 AN: 41144

American (AMR) AF: 0.0000663 AC: 1 AN: 15078

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.000986 AC: 5 AN: 5072

South Asian (SAS) AF: 0.000211 AC: 1 AN: 4742

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10542

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000443 AC: 3 AN: 67702

Other (OTH) AF: 0.00 AC: 0 AN: 2088

⚠️ 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: 0.000119 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	0.082
BayesDel_noAF	Benign	-0.44
CADD	Benign	22
DANN	Benign	0.87
DEOGEN2	Benign	0.00096	T
LIST_S2	Benign	0.85	D
MetaRNN	Benign	0.093	T
PhyloP100		3.1
Sift4G	Benign	0.39	T
Vest4		0.20
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
gMVP		0.22
Mutation Taster		=100/0	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: rs373196176; hg19: chr9-70912520;