chr10-43616369-C-T

Variant names:

• chr10-43616369-C-T
• rs149084067
• NM_145312.4:c.326C>T

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2 BP4_Strong BP6_Moderate

The NM_145312.4(ZNF485):​c.326C>T​(p.Thr109Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000694 in 1,613,866 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.00012 (0 hom., cov: 33)
  • Exomes 𝑓: 0.000064 (0 hom.)
• Consequence: ZNF485 NM_145312.4 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.317

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 Likely_benign. Variant got -4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.037388295).
• BP6: Variant 10-43616369-C-T is Benign according to our data. Variant chr10-43616369-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 3821292.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZNF485	NM_145312.4	c.326C>T	p.Thr109Met	missense_variant	Exon 5 of 5	ENST00000361807.8	NP_660355.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZNF485	ENST00000361807.8	c.326C>T	p.Thr109Met	missense_variant	Exon 5 of 5	1	NM_145312.4	ENSP00000354694.3
ZNF485	ENST00000374435.3	c.326C>T	p.Thr109Met	missense_variant	Exon 5 of 5	1		ENSP00000363558.3
ZNF485	ENST00000430885.5	c.326C>T	p.Thr109Met	missense_variant	Exon 5 of 5	2		ENSP00000393570.1

Frequencies

GnomAD3 genomes AF: 0.000118 AC: 18 AN: 152082 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.0000966

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000393

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000208

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000882

Gnomad OTH AF: 0.000478

GnomAD3 exomes AF: 0.0000996 AC: 25 AN: 251122 Hom.: 0 AF XY: 0.0000884 AC XY: 12 AN XY: 135768

Gnomad AFR exome AF: 0.0000616

Gnomad AMR exome AF: 0.000261

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000981

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000880

Gnomad OTH exome AF: 0.000327

GnomAD4 exome AF: 0.0000643 AC: 94 AN: 1461666 Hom.: 0 Cov.: 36 AF XY: 0.0000523 AC XY: 38 AN XY: 727142

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.000313

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000348

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000594

Gnomad4 OTH exome AF: 0.000166

GnomAD4 genome AF: 0.000118 AC: 18 AN: 152200 Hom.: 0 Cov.: 33 AF XY: 0.000134 AC XY: 10 AN XY: 74410

Gnomad4 AFR AF: 0.0000963

Gnomad4 AMR AF: 0.000393

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000208

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000882

Gnomad4 OTH AF: 0.000473

Alfa AF: 0.0000675 Hom.: 0

Bravo AF: 0.000155

ExAC AF: 0.0000988 AC: 12

EpiCase AF: 0.000109

EpiControl AF: 0.0000593

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Dec 25, 2024

Ambry Genetics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.097
BayesDel_addAF	Benign	-0.52	T
BayesDel_noAF	Benign	-0.69
CADD	Benign	8.5
DANN	Benign	0.30
DEOGEN2	Benign	0.0071	T;T;T
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.4
FATHMM_MKL	Benign	0.00061	N
LIST_S2	Benign	0.42	.;T;T
M_CAP	Benign	0.0019	T
MetaRNN	Benign	0.037	T;T;T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	0.0	N;.;N
PrimateAI	Benign	0.25	T
PROVEAN	Benign	-0.88	N;N;N
REVEL	Benign	0.042
Sift	Benign	0.31	T;T;T
Sift4G	Benign	0.30	T;D;T
Polyphen		1.0	D;.;D
Vest4		0.051
MutPred		0.27		Loss of phosphorylation at T109 (P = 0.0176);Loss of phosphorylation at T109 (P = 0.0176);Loss of phosphorylation at T109 (P = 0.0176);
MVP		0.15
MPC		0.18
ClinPred		0.025	T
GERP RS		-0.28
Varity_R		0.018
gMVP		0.083

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: rs149084067; hg19: chr10-44111817; COSMIC: COSV100700221;