rs377183140

Variant names:

• chr9-41132264-C-A
• rs377183140
• NM_001085457.2:c.1045G>T

Your query was ambiguous. Multiple possible variants found:

• chr9-41132264-C-A
• chr9-41132264-C-T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001085457.2(ZNG1F):​c.1045G>T​(p.Asp349Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000688 in 1,454,444 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 7/10 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 26)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: ZNG1F NM_001085457.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.46
• 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]

ENSG00000308937 (HGNC:):

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

ACMG classification

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

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.21866739).

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.1045G>T	p.Asp349Tyr	missense	Exon 14 of 15	NP_001078926.1	Q4V339
	ZNG1F	NM_001439294.1		c.1030G>T	p.Asp344Tyr	missense	Exon 14 of 15	NP_001426223.1
	ZNG1F	NM_001386876.1		c.985G>T	p.Asp329Tyr	missense	Exon 13 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.1045G>T	p.Asp349Tyr	missense	Exon 14 of 15	ENSP00000366608.4	Q4V339
	ZNG1F	ENST00000456520.5	TSL:1	c.988G>T	p.Asp330Tyr	missense	Exon 13 of 14	ENSP00000401079.2	H0Y5V3
	ZNG1F	ENST00000382436.7	TSL:1	n.*590G>T		non_coding_transcript_exon	Exon 15 of 16	ENSP00000484049.1	A0A087X1C0

Frequencies

GnomAD3 genomes Cov.: 26

GnomAD2 exomes AF: 0.00000428 AC: 1 AN: 233398 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000337

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: 6.88e-7 AC: 1 AN: 1454444 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 723580

African (AFR) AF: 0.00 AC: 0 AN: 33252

American (AMR) AF: 0.0000227 AC: 1 AN: 44088

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26066

East Asian (EAS) AF: 0.00 AC: 0 AN: 39414

South Asian (SAS) AF: 0.00 AC: 0 AN: 85922

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53384

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4110

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1108194

Other (OTH) AF: 0.00 AC: 0 AN: 60014

GnomAD4 genome Cov.: 26

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

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	0.13
BayesDel_noAF	Benign	-0.61
CADD	Benign	23
DANN	Uncertain	0.99
DEOGEN2	Benign	0.021	T
LIST_S2	Uncertain	0.93	D
MetaRNN	Benign	0.22	T
PhyloP100		2.5
Sift4G	Uncertain	0.040	D
Vest4		0.35
gMVP		0.38

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: rs377183140; hg19: chr9-70913973;