Variant 11-65086994-C-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_006782.4(ZFPL1):c.548C>A(p.Ala183Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000415 in 1,613,526 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00026 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000019 ( 0 hom. )

Consequence

ZFPL1
NM_006782.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.328

Variant links:

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]

ZFPL1 links:

TMEM262 (HGNC:):

TMEM262 links:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.013050705).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZFPL1	NM_006782.4 linkuse as main transcript	c.548C>A	p.Ala183Asp	missense_variant	6/8	ENST00000294258.8	NP_006773.2	O95159A0A024R576

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZFPL1	ENST00000294258.8 linkuse as main transcript	c.548C>A	p.Ala183Asp	missense_variant	6/8	1	NM_006782.4	ENSP00000294258.3		O95159

Frequencies

GnomAD3 genomes

AF:

0.000256

AC:

AN:

152138

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000941

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

GnomAD3 exomes

AF:

0.0000604

AC:

AN:

248316

Hom.:

AF XY:

0.0000594

AC XY:

AN XY:

134714

show subpopulations

Gnomad AFR exome

AF:

0.000887

Gnomad AMR exome

AF:

0.0000291

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000192

AC:

AN:

1461270

Hom.:

Cov.:

AF XY:

0.0000179

AC XY:

AN XY:

726940

show subpopulations

Gnomad4 AFR exome

AF:

0.000747

Gnomad4 AMR exome

AF:

0.0000224

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:

0.0000166

GnomAD4 genome

AF:

0.000256

AC:

AN:

152256

Hom.:

Cov.:

AF XY:

0.000255

AC XY:

AN XY:

74424

show subpopulations

Gnomad4 AFR

AF:

0.000938

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

Alfa

AF:

0.0000793

Hom.:

Bravo

AF:

0.000234

ExAC

AF:

0.0000741

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 09, 2024

The c.548C>A (p.A183D) alteration is located in exon 6 (coding exon 5) of the ZFPL1 gene. This alteration results from a C to A substitution at nucleotide position 548, causing the alanine (A) at amino acid position 183 to be replaced by an aspartic acid (D). 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

0.11

BayesDel_addAF

Benign

-0.46

BayesDel_noAF

Benign

-0.49

CADD

Benign

7.7

DANN

Benign

0.96

DEOGEN2

Benign

0.0069

T;T;T

Eigen

Benign

-0.78

Eigen_PC

Benign

-0.69

FATHMM_MKL

Benign

0.24

LIST_S2

Benign

0.65

T;T;T

M_CAP

Benign

0.0079

MetaRNN

Benign

0.013

T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.1

L;.;.

PrimateAI

Benign

0.33

PROVEAN

Benign

-0.70

N;N;N

REVEL

Benign

0.053

Sift

Benign

0.21

T;D;D

Sift4G

Benign

0.38

T;T;T

Polyphen

0.039

B;.;.

Vest4

0.25

MVP

0.043

MPC

0.43

ClinPred

0.024

GERP RS

0.56

Varity_R

0.10

gMVP

0.41

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over