5-43161362-A-C

Position:

• chr5-43161362-A-C

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001330707.2(ZNF131):​c.485A>C​(p.Glu162Ala) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: ZNF131 NM_001330707.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.76

Genes affected

ZNF131 (HGNC:12915): (zinc finger protein 131) Predicted to enable DNA-binding transcription activator activity, RNA polymerase II-specific; DNA-binding transcription repressor activity, RNA polymerase II-specific; and RNA polymerase II cis-regulatory region sequence-specific DNA binding activity. Predicted to be involved in positive regulation of transcription by RNA polymerase II. Located in intermediate filament cytoskeleton and nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.3097875).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNF131	NM_001330707.2	c.485A>C	p.Glu162Ala	missense_variant	5/7	ENST00000682664.1	NP_001317636.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZNF131	ENST00000682664.1	c.485A>C	p.Glu162Ala	missense_variant	5/7		NM_001330707.2	ENSP00000507111	P1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 33

Bravo AF: 0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 20, 2023

The c.485A>C (p.E162A) alteration is located in exon 5 (coding exon 4) of the ZNF131 gene. This alteration results from a A to C substitution at nucleotide position 485, causing the glutamic acid (E) at amino acid position 162 to be replaced by an alanine (A). 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	0.15
BayesDel_addAF	Uncertain	0.034	T
BayesDel_noAF	Benign	-0.19
CADD	Uncertain	25
DANN	Uncertain	0.99
DEOGEN2	Benign	0.063	T;T;.;.;.
Eigen	Uncertain	0.33
Eigen_PC	Uncertain	0.40
FATHMM_MKL	Uncertain	0.97	D
LIST_S2	Uncertain	0.94	D;D;.;.;D
M_CAP	Benign	0.031	D
MetaRNN	Benign	0.31	T;T;T;T;T
MetaSVM	Benign	-0.60	T
MutationAssessor	Benign	1.8	.;L;L;L;L
MutationTaster	Benign	1.0	D;D;D;D;D;D
PrimateAI	Uncertain	0.60	T
PROVEAN	Benign	-1.7	N;N;N;N;N
REVEL	Benign	0.26
Sift	Uncertain	0.024	D;T;T;T;T
Sift4G	Benign	0.28	T;D;D;D;D
Polyphen		0.98, 0.93	.;D;P;P;P
Vest4		0.28, 0.46, 0.41, 0.41
MutPred		0.34		Gain of glycosylation at S160 (P = 0.0805);Gain of glycosylation at S160 (P = 0.0805);Gain of glycosylation at S160 (P = 0.0805);Gain of glycosylation at S160 (P = 0.0805);Gain of glycosylation at S160 (P = 0.0805);
MVP		0.62
MPC		0.48
ClinPred		0.80	D
GERP RS		5.2
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.18
gMVP		0.44

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

Other links and lift over

dbSNP: rs1749674144; hg19: chr5-43161464;