4-112541135-C-A

Variant names:

• chr4-112541135-C-A
• NM_018392.5:c.5732G>T

Variant summary

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

The NM_018392.5(ZGRF1):​c.5732G>T​(p.Trp1911Leu) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: ZGRF1 NM_018392.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.38
• Publications: 0 publications found

Genes affected

ZGRF1 (HGNC:25654): (zinc finger GRF-type containing 1) The encoded protein contains GRF zinc finger (zf-GRF) and transmembrane domains. GRF zinc fingers are found in a number of DNA-binding proteins. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Apr 2017]

NEUROG2-AS1 (HGNC:40656): (NEUROG2 and ZGRF1 antisense RNA 1)

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_018392.5. 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
	ZGRF1	NM_018392.5	MANE Select	c.5732G>T	p.Trp1911Leu	missense	Exon 25 of 28	NP_060862.3
	ZGRF1	NM_001350397.2		c.5558G>T	p.Trp1853Leu	missense	Exon 24 of 27	NP_001337326.1
	NEUROG2-AS1	NR_161159.1		n.513-5650C>A		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZGRF1	ENST00000505019.6	TSL:5 MANE Select	c.5732G>T	p.Trp1911Leu	missense	Exon 25 of 28	ENSP00000424737.1	Q86YA3-1
	ZGRF1	ENST00000445203.6	TSL:5	c.5732G>T	p.Trp1911Leu	missense	Exon 24 of 27	ENSP00000390505.3	Q86YA3-1
	ZGRF1	ENST00000925931.1		c.5558G>T	p.Trp1853Leu	missense	Exon 24 of 27	ENSP00000595990.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

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	Pathogenic	0.83
BayesDel_addAF	Uncertain	0.072	D
BayesDel_noAF	Benign	-0.13
CADD	Pathogenic	26
DANN	Benign	0.97
DEOGEN2	Uncertain	0.66	D
Eigen	Uncertain	0.43
Eigen_PC	Uncertain	0.53
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Uncertain	0.87	D
M_CAP	Uncertain	0.11	D
MetaRNN	Uncertain	0.56	D
MetaSVM	Uncertain	0.64	D
MutationAssessor	Benign	0.81	L
PhyloP100		5.4
PROVEAN	Pathogenic	-6.0	D
REVEL	Uncertain	0.51
Sift	Benign	0.036	D
Sift4G	Benign	0.19	T
Vest4		0.56
MutPred		0.52		Loss of catalytic residue at L1909 (P = 0.0054)
MVP		0.63
MPC		0.52
ClinPred		0.98	D
GERP RS		5.8
Varity_R		0.64
gMVP		0.56
Mutation Taster		=76/24	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

hg19: chr4-113462291;