chr9-41133718-C-G

Variant names:

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

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 0P and 1B. BP4

The NM_001085457.2(ZNG1F):​c.841G>C​(p.Val281Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 8/10 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V281I) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.0000066 (0 hom., cov: 28)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: ZNG1F NM_001085457.2 missense
• Clinical Significance: Not reported in ClinVar
• 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 -1 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.27020794).

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>C	p.Val281Leu	missense	Exon 12 of 15	NP_001078926.1	Q4V339
	ZNG1F	NM_001439294.1		c.826G>C	p.Val276Leu	missense	Exon 12 of 15	NP_001426223.1
	ZNG1F	NM_001386876.1		c.781G>C	p.Val261Leu	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>C	p.Val281Leu	missense	Exon 12 of 15	ENSP00000366608.4	Q4V339
	ZNG1F	ENST00000456520.5	TSL:1	c.784G>C	p.Val262Leu	missense	Exon 11 of 14	ENSP00000401079.2	H0Y5V3
	ZNG1F	ENST00000382436.7	TSL:1	n.*386G>C		non_coding_transcript_exon	Exon 13 of 16	ENSP00000484049.1	A0A087X1C0

Frequencies

GnomAD3 genomes AF: 0.00000662 AC: 1 AN: 150952 Hom.: 0 Cov.: 28

Gnomad AFR AF: 0.0000244

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

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

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 6.92e-7 AC: 1 AN: 1444216 Hom.: 0 Cov.: 41 AF XY: 0.00 AC XY: 0 AN XY: 718854

⚠️ 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: 33358

American (AMR) AF: 0.00 AC: 0 AN: 44602

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 39586

South Asian (SAS) AF: 0.00 AC: 0 AN: 86112

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

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4130

European-Non Finnish (NFE) AF: 9.00e-7 AC: 1 AN: 1111126

Other (OTH) AF: 0.00 AC: 0 AN: 60056

⚠️ 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: 0.00000662 AC: 1 AN: 150952 Hom.: 0 Cov.: 28 AF XY: 0.0000136 AC XY: 1 AN XY: 73680

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

African (AFR) AF: 0.0000244 AC: 1 AN: 41050

American (AMR) AF: 0.00 AC: 0 AN: 15060

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 5080

South Asian (SAS) AF: 0.00 AC: 0 AN: 4746

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

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 67712

Other (OTH) AF: 0.00 AC: 0 AN: 2066

⚠️ 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

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.27
BayesDel_noAF	Benign	-0.44
CADD	Benign	21
DANN	Benign	0.83
DEOGEN2	Benign	0.0035	T
LIST_S2	Uncertain	0.91	D
MetaRNN	Benign	0.27	T
PhyloP100		3.1
Sift4G	Benign	0.65	T
Vest4		0.47
gMVP		0.44

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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;