rs373196176

Variant names:

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

Your query was ambiguous. Multiple possible variants found:

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

Variant summary

Our verdict is Likely benign. Variant got -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. 7/10 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

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

Verdict is Likely_benign. Variant got -1 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZNG1F	NM_001085457.2	c.841G>C	p.Val281Leu	missense_variant	Exon 12 of 15	ENST00000377391.8	NP_001078926.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZNG1F	ENST00000377391.8	c.841G>C	p.Val281Leu	missense_variant	Exon 12 of 15	1	NM_001085457.2	ENSP00000366608.4
ZNG1F	ENST00000456520.5	c.784G>C	p.Val262Leu	missense_variant	Exon 11 of 14	1		ENSP00000401079.2
ZNG1F	ENST00000382436.7	n.*386G>C		non_coding_transcript_exon_variant	Exon 13 of 16	1		ENSP00000484049.1
ZNG1F	ENST00000486387.6	n.*1406G>C		non_coding_transcript_exon_variant	Exon 14 of 17	2		ENSP00000480837.1
ZNG1F	ENST00000382436.7	n.*386G>C		3_prime_UTR_variant	Exon 13 of 16	1		ENSP00000484049.1
ZNG1F	ENST00000486387.6	n.*1406G>C		3_prime_UTR_variant	Exon 14 of 17	2		ENSP00000480837.1

Frequencies

GnomAD3 genomes AF: 0.00 AC: 1 AN: 150952 Hom.: 0 Cov.: 28 FAILED QC

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

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 9.00e-7

Gnomad4 OTH exome AF: 0.00

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

Gnomad4 AFR AF: 0.0000244

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00

Gnomad4 OTH AF: 0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

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;D;D
MetaRNN	Benign	0.27	T;T;T
Sift4G	Benign	0.65	T;T;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

Publications

LitVar

Other links and lift over

dbSNP: rs373196176; hg19: chr9-70912520;