10-43616384-T-C

Position:

• chr10-43616384-T-C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_145312.4(ZNF485):​c.341T>C​(p.Met114Thr) 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. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: ZNF485 NM_145312.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.116

Genes affected

ZNF485 (HGNC:23440): (zinc finger protein 485) Predicted to enable DNA-binding transcription activator activity, RNA polymerase II-specific and RNA polymerase II cis-regulatory region sequence-specific DNA binding activity. Predicted to be involved in regulation of transcription by RNA polymerase II. Predicted to be active in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.085146844).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNF485	NM_145312.4	c.341T>C	p.Met114Thr	missense_variant	5/5	ENST00000361807.8	NP_660355.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZNF485	ENST00000361807.8	c.341T>C	p.Met114Thr	missense_variant	5/5	1	NM_145312.4	ENSP00000354694.3
ZNF485	ENST00000374435.3	c.341T>C	p.Met114Thr	missense_variant	5/5	1		ENSP00000363558.3
ZNF485	ENST00000430885.5	c.341T>C	p.Met114Thr	missense_variant	5/5	2		ENSP00000393570.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 36

GnomAD4 genome Cov.: 33

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 02, 2022

The c.341T>C (p.M114T) alteration is located in exon 5 (coding exon 4) of the ZNF485 gene. This alteration results from a T to C substitution at nucleotide position 341, causing the methionine (M) at amino acid position 114 to be replaced by a threonine (T). 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	0.091
BayesDel_addAF	Benign	-0.26	T
BayesDel_noAF	Benign	-0.60
CADD	Benign	2.6
DANN	Benign	0.38
DEOGEN2	Benign	0.0090	T;T;T
Eigen	Benign	-0.84
Eigen_PC	Benign	-0.92
FATHMM_MKL	Benign	0.0011	N
LIST_S2	Benign	0.29	.;T;T
M_CAP	Benign	0.0025	T
MetaRNN	Benign	0.085	T;T;T
MetaSVM	Benign	-0.92	T
MutationAssessor	Benign	0.69	N;.;N
PrimateAI	Benign	0.36	T
PROVEAN	Benign	-0.75	N;N;N
REVEL	Benign	0.041
Sift	Benign	0.48	T;D;T
Sift4G	Benign	0.41	T;D;T
Polyphen		0.67	P;.;P
Vest4		0.13
MutPred		0.25		Loss of stability (P = 0.0371);Loss of stability (P = 0.0371);Loss of stability (P = 0.0371);
MVP		0.15
MPC		0.14
ClinPred		0.16	T
GERP RS		1.8
Varity_R		0.061
gMVP		0.11

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr10-44111832;