20-59191096-C-G

Variant names:

• chr20-59191096-C-G
• rs774065552
• NM_178457.3:c.77C>G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_178457.3(ZNF831):​c.77C>G​(p.Ala26Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A26V) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 33)
• Consequence: ZNF831 NM_178457.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.127
• Publications: 0 publications found

Genes affected

ZNF831 (HGNC:16167): (zinc finger protein 831) Predicted to enable metal ion binding activity. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

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

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.034957975).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_178457.3. 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
	ZNF831	NM_178457.3	MANE Select	c.77C>G	p.Ala26Gly	missense	Exon 2 of 6	NP_848552.1	Q5JPB2
	ZNF831	NM_001384354.1		c.77C>G	p.Ala26Gly	missense	Exon 4 of 8	NP_001371283.1	Q5JPB2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZNF831	ENST00000371030.4	TSL:1 MANE Select	c.77C>G	p.Ala26Gly	missense	Exon 2 of 6	ENSP00000360069.2	Q5JPB2
	ZNF831	ENST00000637017.1	TSL:5	c.77C>G	p.Ala26Gly	missense	Exon 4 of 8	ENSP00000490240.1	Q5JPB2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.38	T
BayesDel_noAF	Benign	-0.79
CADD	Benign	15
DANN	Benign	0.96
DEOGEN2	Benign	0.0068	T
Eigen	Benign	-0.92
Eigen_PC	Benign	-0.84
FATHMM_MKL	Benign	0.11	N
LIST_S2	Benign	0.52	T
M_CAP	Benign	0.0079	T
MetaRNN	Benign	0.035	T
MetaSVM	Benign	-0.94	T
MutationAssessor	Benign	1.7	L
PhyloP100		-0.13
PrimateAI	Benign	0.37	T
PROVEAN	Benign	-1.8	N
REVEL	Benign	0.020
Sift	Benign	0.39	T
Sift4G	Benign	0.34	T
Polyphen		0.034	B
Vest4		0.11
MutPred		0.20		Gain of catalytic residue at A26 (P = 0.0898)
MVP		0.030
MPC		0.32
ClinPred		0.056	T
GERP RS		2.1
Varity_R		0.048
gMVP		0.27
Mutation Taster		=95/5	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: rs774065552; hg19: chr20-57766151;