Genetic Variant NM_182491.4:c.230G>C (chr7-1155505-C-G) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_182491.4(ZFAND2A):c.230G>C(p.Gly77Ala) variant causes a missense change. The variant allele was found at a frequency of 0.00000958 in 1,461,746 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/22 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: 0.0000096 ( 0 hom. )

Consequence

ZFAND2A
NM_182491.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.84

Publications

0 publications found

Variant links:

Genes affected

ZFAND2A (HGNC:28073): (zinc finger AN1-type containing 2A) Predicted to enable zinc ion binding activity. Predicted to be involved in proteasome-mediated ubiquitin-dependent protein catabolic process and protein targeting to ER. Predicted to act upstream of or within cellular response to arsenic-containing substance and positive regulation of proteasomal ubiquitin-dependent protein catabolic process. Predicted to be located in nucleus. Predicted to be part of proteasome complex. Predicted to be active in endoplasmic reticulum. [provided by Alliance of Genome Resources, Apr 2022]

ZFAND2A links:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.16424772).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_182491.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ZFAND2A	NM_182491.4	MANE Select	c.230G>C	p.Gly77Ala	missense	Exon 4 of 5	NP_872297.2	Q8N6M9
ZFAND2A	NM_001365383.1		c.230G>C	p.Gly77Ala	missense	Exon 4 of 6	NP_001352312.1	J3KQ25
ZFAND2A	NM_001365381.2		c.230G>C	p.Gly77Ala	missense	Exon 4 of 5	NP_001352310.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ZFAND2A	ENST00000316495.8	TSL:1 MANE Select	c.230G>C	p.Gly77Ala	missense	Exon 4 of 5	ENSP00000314619.3	Q8N6M9
ZFAND2A	ENST00000397083.6	TSL:1	c.230G>C	p.Gly77Ala	missense	Exon 4 of 5	ENSP00000380273.1	A8MYA3
ZFAND2A	ENST00000401903.6	TSL:3	c.230G>C	p.Gly77Ala	missense	Exon 4 of 6	ENSP00000386031.1	J3KQ25

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.0000398

AC:

AN:

251470

AF XY:

0.0000294

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000544

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000958

AC:

AN:

1461746

Hom.:

Cov.:

AF XY:

0.00000825

AC XY:

AN XY:

727192

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33480

American (AMR)

AF:

0.00

AC:

AN:

44716

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26130

East Asian (EAS)

AF:

0.000252

AC:

AN:

39692

South Asian (SAS)

AF:

0.0000232

AC:

AN:

86254

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53406

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1111922

Other (OTH)

AF:

0.0000331

AC:

AN:

60378

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.468

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000756

ExAC

AF:

0.0000412

AC:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.18

BayesDel_addAF

Benign

-0.39

BayesDel_noAF

Benign

-0.44

CADD

Benign

(source)

DANN

Benign

0.88

DEOGEN2

Benign

0.12

Eigen

Benign

-0.041

Eigen_PC

Benign

-0.11

FATHMM_MKL

Uncertain

0.95

LIST_S2

Pathogenic

0.99

M_CAP

Benign

0.0076

MetaRNN

Benign

0.16

MetaSVM

Benign

-0.83

MutationAssessor

Pathogenic

3.0

PhyloP100

6.8

PrimateAI

Benign

0.32

PROVEAN

Pathogenic

-4.6

REVEL

Benign

0.27

Sift

Uncertain

0.0080

Sift4G

Benign

0.090

Polyphen

0.45

Vest4

0.56

MutPred

0.36

Loss of disorder (P = 0.1009)

MVP

0.27

MPC

0.021

ClinPred

0.53

GERP RS

4.5

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.31

gMVP

0.13

Mutation Taster

=86/14

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over