11-65086592-G-T

Position:

• chr11-65086592-G-T

Variant summary

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

The NM_006782.4(ZFPL1):​c.392G>T​(p.Gly131Val) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,710 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: ZFPL1 NM_006782.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 8.90

Genes affected

ZFPL1 (HGNC:12868): (zinc finger protein like 1) Predicted to enable metal ion binding activity. Predicted to be involved in vesicle-mediated transport. Located in Golgi apparatus. [provided by Alliance of Genome Resources, Apr 2022]

TMEM262 (HGNC:):

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/exons	MANE	Protein	UniProt
ZFPL1	NM_006782.4	c.392G>T	p.Gly131Val	missense_variant	4/8	ENST00000294258.8	NP_006773.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZFPL1	ENST00000294258.8	c.392G>T	p.Gly131Val	missense_variant	4/8	1	NM_006782.4	ENSP00000294258.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461710 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 727142

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: 0.0000116

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

Jul 19, 2023

The c.392G>T (p.G131V) alteration is located in exon 4 (coding exon 3) of the ZFPL1 gene. This alteration results from a G to T substitution at nucleotide position 392, causing the glycine (G) at amino acid position 131 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	Pathogenic	0.67
BayesDel_addAF	Pathogenic	0.27	D
BayesDel_noAF	Pathogenic	0.14
CADD	Pathogenic	32
DANN	Uncertain	1.0
DEOGEN2	Benign	0.12	T;T;T;T
Eigen	Pathogenic	0.71
Eigen_PC	Pathogenic	0.72
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.94	D;D;D;D
M_CAP	Benign	0.046	D
MetaRNN	Uncertain	0.69	D;D;D;D
MetaSVM	Benign	-0.86	T
MutationAssessor	Uncertain	2.0	M;.;.;.
PrimateAI	Uncertain	0.70	T
PROVEAN	Pathogenic	-7.4	D;D;D;D
REVEL	Uncertain	0.53
Sift	Uncertain	0.0030	D;D;D;T
Sift4G	Uncertain	0.0080	D;T;T;T
Polyphen		1.0	D;.;.;.
Vest4		0.95
MutPred		0.44		Loss of loop (P = 0.0512);Loss of loop (P = 0.0512);.;Loss of loop (P = 0.0512);
MVP		0.15
MPC		1.1
ClinPred		1.0	D
GERP RS		5.4
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
Varity_R		0.89
gMVP		0.77

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: chr11-64854064;