rs915106672

Variant names:

• chr7-1155531-C-G
• rs915106672
• NM_182491.4:c.204G>C

Your query was ambiguous. Multiple possible variants found:

• chr7-1155531-C-G
• chr7-1155531-C-T

Variant summary

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

The NM_182491.4(ZFAND2A):​c.204G>C​(p.Lys68Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000155 in 1,613,750 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: 𝑓 0.000079 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0000089 (0 hom.)
• Consequence: ZFAND2A NM_182491.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.895
• Publications: 0 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 -2 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.1596689).

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.204G>C	p.Lys68Asn	missense	Exon 4 of 5	NP_872297.2	Q8N6M9
	ZFAND2A	NM_001365383.1		c.204G>C	p.Lys68Asn	missense	Exon 4 of 6	NP_001352312.1	J3KQ25
	ZFAND2A	NM_001365381.2		c.204G>C	p.Lys68Asn	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.204G>C	p.Lys68Asn	missense	Exon 4 of 5	ENSP00000314619.3	Q8N6M9
	ZFAND2A	ENST00000397083.6	TSL:1	c.204G>C	p.Lys68Asn	missense	Exon 4 of 5	ENSP00000380273.1	A8MYA3
	ZFAND2A	ENST00000401903.6	TSL:3	c.204G>C	p.Lys68Asn	missense	Exon 4 of 6	ENSP00000386031.1	J3KQ25

Frequencies

GnomAD3 genomes AF: 0.0000789 AC: 12 AN: 152048 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000242

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000655

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: 0.000478

GnomAD2 exomes AF: 0.00000795 AC: 2 AN: 251456 AF XY: 0.0000147

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000289

Gnomad ASJ exome AF: 0.00

Gnomad EAS 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: 0.00000889 AC: 13 AN: 1461702 Hom.: 0 Cov.: 30 AF XY: 0.00000963 AC XY: 7 AN XY: 727162

African (AFR) AF: 0.0000299 AC: 1 AN: 33478

American (AMR) AF: 0.000134 AC: 6 AN: 44714

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26130

East Asian (EAS) AF: 0.00 AC: 0 AN: 39692

South Asian (SAS) AF: 0.0000116 AC: 1 AN: 86254

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53404

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1111888

Other (OTH) AF: 0.0000828 AC: 5 AN: 60374

GnomAD4 genome AF: 0.0000789 AC: 12 AN: 152048 Hom.: 0 Cov.: 32 AF XY: 0.000121 AC XY: 9 AN XY: 74266

African (AFR) AF: 0.0000242 AC: 1 AN: 41386

American (AMR) AF: 0.000655 AC: 10 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5190

South Asian (SAS) AF: 0.00 AC: 0 AN: 4806

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10602

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

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68000

Other (OTH) AF: 0.000478 AC: 1 AN: 2094

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.000121

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	0.30
BayesDel_addAF	Benign	-0.31	T
BayesDel_noAF	Benign	-0.59
CADD	Benign	20
DANN	Uncertain	0.99
DEOGEN2	Benign	0.071	T
Eigen	Benign	0.064
Eigen_PC	Benign	-0.036
FATHMM_MKL	Uncertain	0.86	D
LIST_S2	Uncertain	0.92	D
M_CAP	Benign	0.0077	T
MetaRNN	Benign	0.16	T
MetaSVM	Benign	-0.90	T
MutationAssessor	Uncertain	2.5	M
PhyloP100		0.90
PrimateAI	Benign	0.31	T
PROVEAN	Uncertain	-2.5	D
REVEL	Benign	0.13
Sift	Uncertain	0.0070	D
Sift4G	Benign	0.062	T
Polyphen		0.94	P
Vest4		0.34
MutPred		0.44		Loss of methylation at K68 (P = 6e-04)
MVP		0.19
MPC		0.015
ClinPred		0.80	D
GERP RS		3.6
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.15
gMVP		0.16
Mutation Taster		=82/18	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: rs915106672; hg19: chr7-1195167;