9-41183657-C-T

Variant names:

• chr9-41183657-C-T
• rs748958590
• NM_001085457.2:c.245G>A

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_001085457.2(ZNG1F):​c.245G>A​(p.Ser82Asn) variant causes a missense change. The variant allele was found at a frequency of 0.00000412 in 1,456,160 control chromosomes in the GnomAD database, including 1 homozygotes. 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. S82I) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 27)
  • Exomes 𝑓: 0.0000041 (1 hom.)
• Consequence: ZNG1F NM_001085457.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 6.91
• 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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

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.245G>A	p.Ser82Asn	missense	Exon 3 of 15	NP_001078926.1	Q4V339
	ZNG1F	NM_001439294.1		c.245G>A	p.Ser82Asn	missense	Exon 3 of 15	NP_001426223.1
	ZNG1F	NM_001386876.1		c.245G>A	p.Ser82Asn	missense	Exon 3 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.245G>A	p.Ser82Asn	missense	Exon 3 of 15	ENSP00000366608.4	Q4V339
	ZNG1F	ENST00000456520.5	TSL:1	c.245G>A	p.Ser82Asn	missense	Exon 3 of 14	ENSP00000401079.2	H0Y5V3
	ZNG1F	ENST00000382436.7	TSL:1	n.113G>A		non_coding_transcript_exon	Exon 3 of 16	ENSP00000484049.1	A0A087X1C0

Frequencies

GnomAD3 genomes Cov.: 27

GnomAD2 exomes AF: 0.00000400 AC: 1 AN: 249784 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

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 AF: 0.00000412 AC: 6 AN: 1456160 Hom.: 1 Cov.: 34 AF XY: 0.00000414 AC XY: 3 AN XY: 724450

African (AFR) AF: 0.00 AC: 0 AN: 33290

American (AMR) AF: 0.00 AC: 0 AN: 44056

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26064

East Asian (EAS) AF: 0.00 AC: 0 AN: 39382

South Asian (SAS) AF: 0.0000465 AC: 4 AN: 85960

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53368

Middle Eastern (MID) AF: 0.000349 AC: 2 AN: 5726

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1108156

Other (OTH) AF: 0.00 AC: 0 AN: 60158

GnomAD4 genome Cov.: 27

Alfa AF: 0.0000225 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.16
BayesDel_noAF	Benign	-0.20
CADD	Benign	21
DANN	Benign	0.96
DEOGEN2	Benign	0.0053	T
LIST_S2	Benign	0.68	T
MetaRNN	Uncertain	0.67	D
PhyloP100		6.9
Sift4G	Benign	0.52	T
Vest4		0.73
gMVP		0.48
Mutation Taster		=99/1	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: rs748958590; hg19: chr9-70862532;