9-41183584-A-C

Variant names:

• chr9-41183584-A-C
• rs1427986567
• NM_001085457.2:c.318T>G

Variant summary

Our verdict is Benign. The variant received -7 ACMG points: 0P and 7B. BP4_Strong BP6_Moderate BP7

The NM_001085457.2(ZNG1F):​c.318T>G​(p.Gly106Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: not found (cov: 19)
  • Exomes 𝑓: 0.0000055 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: ZNG1F NM_001085457.2 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.42
• 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: Benign. The variant received -7 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.56).
• BP6: Variant 9-41183584-A-C is Benign according to our data. Variant chr9-41183584-A-C is described in ClinVar as Likely_benign. ClinVar VariationId is 2659230.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=1.42 with no splicing effect.

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.318T>G	p.Gly106Gly	synonymous	Exon 3 of 15	NP_001078926.1	Q4V339
	ZNG1F	NM_001439294.1		c.318T>G	p.Gly106Gly	synonymous	Exon 3 of 15	NP_001426223.1
	ZNG1F	NM_001386876.1		c.318T>G	p.Gly106Gly	synonymous	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.318T>G	p.Gly106Gly	synonymous	Exon 3 of 15	ENSP00000366608.4	Q4V339
	ZNG1F	ENST00000456520.5	TSL:1	c.318T>G	p.Gly106Gly	synonymous	Exon 3 of 14	ENSP00000401079.2	H0Y5V3
	ZNG1F	ENST00000382436.7	TSL:1	n.186T>G		non_coding_transcript_exon	Exon 3 of 16	ENSP00000484049.1	A0A087X1C0

Frequencies

GnomAD3 genomes Cov.: 19

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00000550 AC: 8 AN: 1455152 Hom.: 0 Cov.: 30 AF XY: 0.00000414 AC XY: 3 AN XY: 723992

⚠️ 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: 33234

American (AMR) AF: 0.00 AC: 0 AN: 43936

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26036

East Asian (EAS) AF: 0.00 AC: 0 AN: 39350

South Asian (SAS) AF: 0.0000116 AC: 1 AN: 85906

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53340

Middle Eastern (MID) AF: 0.000176 AC: 1 AN: 5696

European-Non Finnish (NFE) AF: 0.00000542 AC: 6 AN: 1107546

Other (OTH) AF: 0.00 AC: 0 AN: 60108

⚠️ 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 Cov.: 19

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.56
CADD	Benign	9.7
DANN	Benign	0.81
PhyloP100		1.4

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.12		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: rs1427986567; hg19: chr9-70862605;