NM_001085457.2:c.445A>T

Variant names:

• chr9-41174338-T-A
• rs776177539
• NM_001085457.2:c.445A>T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001085457.2(ZNG1F):​c.445A>T​(p.Met149Leu) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. 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. M149V) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 26)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: ZNG1F NM_001085457.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.08

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 Uncertain_significance. Variant got 2 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZNG1F	NM_001085457.2	c.445A>T	p.Met149Leu	missense_variant	Exon 5 of 15	ENST00000377391.8	NP_001078926.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZNG1F	ENST00000377391.8	c.445A>T	p.Met149Leu	missense_variant	Exon 5 of 15	1	NM_001085457.2	ENSP00000366608.4
ZNG1F	ENST00000456520.5	c.445A>T	p.Met149Leu	missense_variant	Exon 5 of 14	1		ENSP00000401079.2
ZNG1F	ENST00000382436.7	n.313A>T		non_coding_transcript_exon_variant	Exon 5 of 16	1		ENSP00000484049.1
ZNG1F	ENST00000467791.5	n.34A>T		non_coding_transcript_exon_variant	Exon 2 of 10	5		ENSP00000480830.1
ZNG1F	ENST00000486387.6	n.445A>T		non_coding_transcript_exon_variant	Exon 5 of 17	2		ENSP00000480837.1

Frequencies

GnomAD3 genomes Cov.: 26

GnomAD3 exomes AF: 0.0000290 AC: 4 AN: 137716 Hom.: 0 AF XY: 0.0000261 AC XY: 2 AN XY: 76626

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000177

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.000169

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AC0;AS_VQSR AF: 0.00 AC: 0 AN: 1445208 Hom.: 0 Cov.: 36 AF XY: 0.00 AC XY: 0 AN XY: 718526

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: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 26

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_noAF	Benign	-0.35
CADD	Benign	20
DANN	Benign	0.77
DEOGEN2	Benign	0.0064	.;T;.;.
LIST_S2	Benign	0.82	T;T;D;D
MetaRNN	Uncertain	0.53	D;D;D;D
PROVEAN	Benign	-0.27	.;N;N;.
Sift	Benign	0.72	.;T;T;.
Sift4G	Benign	0.60	T;T;T;T
Vest4		0.65
gMVP		0.44

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

Publications

LitVar

Other links and lift over

dbSNP: rs776177539; hg19: chr9-70871851;