chr4-112548335-T-C

Position:

• chr4-112548335-T-C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_018392.5(ZGRF1):​c.5392A>G​(p.Met1798Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000713 in 1,402,442 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 7.1e-7 (0 hom.)
• Consequence: ZGRF1 NM_018392.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.569

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]

ZGRF1 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.23468405).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZGRF1	NM_018392.5	c.5392A>G	p.Met1798Val	missense_variant	23/28	ENST00000505019.6	NP_060862.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZGRF1	ENST00000505019.6	c.5392A>G	p.Met1798Val	missense_variant	23/28	5	NM_018392.5	ENSP00000424737.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 7.13e-7 AC: 1 AN: 1402442 Hom.: 0 Cov.: 29 AF XY: 0.00 AC XY: 0 AN XY: 691954

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000278

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.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jan 18, 2022

The c.5392A>G (p.M1798V) alteration is located in exon 23 (coding exon 22) of the ZGRF1 gene. This alteration results from a A to G substitution at nucleotide position 5392, causing the methionine (M) at amino acid position 1798 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.20
BayesDel_addAF	Benign	-0.047	T
BayesDel_noAF	Benign	-0.30
CADD	Benign	17
DANN	Benign	0.95
DEOGEN2	Benign	0.29	T;T
Eigen	Benign	-0.18
Eigen_PC	Benign	-0.091
FATHMM_MKL	Benign	0.69	D
LIST_S2	Benign	0.81	T;.
M_CAP	Benign	0.055	D
MetaRNN	Benign	0.23	T;T
MetaSVM	Benign	-0.55	T
MutationAssessor	Uncertain	2.3	M;M
PROVEAN	Benign	-1.7	.;N
REVEL	Benign	0.18
Sift	Benign	0.037	.;D
Sift4G	Uncertain	0.019	D;D
Vest4		0.32
MutPred		0.35		Loss of methylation at K1802 (P = 0.1388);Loss of methylation at K1802 (P = 0.1388);
MVP		0.50
MPC		0.14
ClinPred		0.58	D
GERP RS		2.0
Varity_R		0.092
gMVP		0.35

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr4-113469491;