7-1155469-C-G

Variant names:

• chr7-1155469-C-G
• rs370480157
• NM_182491.4:c.266G>C

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_182491.4(ZFAND2A):​c.266G>C​(p.Gly89Ala) variant causes a missense change. The variant allele was found at a frequency of 0.000138 in 1,613,570 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00012 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00014 (0 hom.)
• Consequence: ZFAND2A NM_182491.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.07
• Publications: 2 publications found

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]

ACMG classification

Our verdict: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.043833613).

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZFAND2A	NM_182491.4	MANE Select	c.266G>C	p.Gly89Ala	missense	Exon 4 of 5	NP_872297.2	Q8N6M9
	ZFAND2A	NM_001365383.1		c.266G>C	p.Gly89Ala	missense	Exon 4 of 6	NP_001352312.1	J3KQ25
	ZFAND2A	NM_001365381.2		c.266G>C	p.Gly89Ala	missense	Exon 4 of 5	NP_001352310.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZFAND2A	ENST00000316495.8	TSL:1 MANE Select	c.266G>C	p.Gly89Ala	missense	Exon 4 of 5	ENSP00000314619.3	Q8N6M9
	ZFAND2A	ENST00000397083.6	TSL:1	c.266G>C	p.Gly89Ala	missense	Exon 4 of 5	ENSP00000380273.1	A8MYA3
	ZFAND2A	ENST00000401903.6	TSL:3	c.266G>C	p.Gly89Ala	missense	Exon 4 of 6	ENSP00000386031.1	J3KQ25

Frequencies

GnomAD3 genomes AF: 0.000118 AC: 18 AN: 152092 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000725

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: 0.000221

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000995 AC: 25 AN: 251378 AF XY: 0.0000442

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000220

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.000140 AC: 205 AN: 1461478 Hom.: 0 Cov.: 30 AF XY: 0.000121 AC XY: 88 AN XY: 727064

African (AFR) AF: 0.0000299 AC: 1 AN: 33472

American (AMR) AF: 0.0000224 AC: 1 AN: 44694

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26126

East Asian (EAS) AF: 0.00 AC: 0 AN: 39678

South Asian (SAS) AF: 0.00 AC: 0 AN: 86230

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53368

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5758

European-Non Finnish (NFE) AF: 0.000178 AC: 198 AN: 1111788

Other (OTH) AF: 0.0000828 AC: 5 AN: 60364

GnomAD4 genome AF: 0.000118 AC: 18 AN: 152092 Hom.: 0 Cov.: 32 AF XY: 0.000108 AC XY: 8 AN XY: 74308

African (AFR) AF: 0.0000725 AC: 3 AN: 41390

American (AMR) AF: 0.00 AC: 0 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5198

South Asian (SAS) AF: 0.00 AC: 0 AN: 4826

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10610

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.000221 AC: 15 AN: 68008

Other (OTH) AF: 0.00 AC: 0 AN: 2086

Alfa AF: 0.000158 Hom.: 0

Bravo AF: 0.000106

TwinsUK AF: 0.000270 AC: 1

ALSPAC AF: 0.00 AC: 0

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000116 AC: 1

ExAC AF: 0.0000741 AC: 9

EpiCase AF: 0.000109

EpiControl AF: 0.000237

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	Benign	0.095
BayesDel_addAF	Benign	-0.38	T
BayesDel_noAF	Benign	-0.49
CADD	Benign	3.8
DANN	Benign	0.59
DEOGEN2	Benign	0.0028	T
Eigen	Benign	-0.82
Eigen_PC	Benign	-0.74
FATHMM_MKL	Benign	0.44	N
LIST_S2	Benign	0.65	T
M_CAP	Benign	0.0030	T
MetaRNN	Benign	0.044	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.81	L
PhyloP100		4.1
PrimateAI	Benign	0.26	T
PROVEAN	Benign	1.1	N
REVEL	Benign	0.12
Sift	Benign	1.0	T
Sift4G	Benign	1.0	T
Polyphen		0.040	B
Vest4		0.17
MVP		0.16
MPC		0.0086
ClinPred		0.030	T
GERP RS		2.3
Varity_R		0.042
gMVP		0.12
Mutation Taster		=93/7	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

dbSNP: rs370480157; hg19: chr7-1195105;