rs113884485

Variant names:

• chr4-373417-C-G
• rs113884485
• NM_003441.4:c.980C>G

Your query was ambiguous. Multiple possible variants found:

• chr4-373417-C-G
• chr4-373417-C-T

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 2P and 12B. PM2 BP4_Strong BP6_Very_Strong

The NM_003441.4(ZNF141):​c.980C>G​(p.Thr327Ser) 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 Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0 (0 hom., cov: 33)
  • Failed GnomAD Quality Control
• Consequence: ZNF141 NM_003441.4 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.32
• Publications: 9 publications found

Genes affected

ZNF141 (HGNC:12926): (zinc finger protein 141) The protein encoded by this gene is a zinc finger protein that may be a tumor suppressor. Defects in this gene have been associated with autosomal recessive postaxial polydactyly type A. [provided by RefSeq, Jan 2017]

ZNF141 Gene-Disease associations (from GenCC):

• postaxial polydactyly type A

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
• polydactyly, postaxial, type A6

  Inheritance: AR Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -10 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.002601862).
• BP6: Variant 4-373417-C-G is Benign according to our data. Variant chr4-373417-C-G is described in ClinVar as Benign. ClinVar VariationId is 403623.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003441.4. 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
	ZNF141	NM_003441.4	MANE Select	c.980C>G	p.Thr327Ser	missense	Exon 4 of 4	NP_003432.1	Q15928
	ZNF141	NM_001348277.2		c.752C>G	p.Thr251Ser	missense	Exon 2 of 2	NP_001335206.1	Q4W5N2
	ZNF141	NM_001348278.2		c.570+410C>G		intron	N/A	NP_001335207.1	D6RIY0

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZNF141	ENST00000240499.8	TSL:1 MANE Select	c.980C>G	p.Thr327Ser	missense	Exon 4 of 4	ENSP00000240499.7	Q15928
	ZNF141	ENST00000512994.5	TSL:1	c.570+410C>G		intron	N/A	ENSP00000425799.1	D6RIY0
	ZNF141	ENST00000885054.1		c.1115C>G	p.Thr372Ser	missense	Exon 5 of 5	ENSP00000555113.1

Frequencies

GnomAD3 genomes AF: 0.00 AC: 0 AN: 149714 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

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: 0.00

GnomAD2 exomes AF: 0.0000908 AC: 11 AN: 121096 AF XY: 0.000107

Gnomad AFR exome AF: 0.0000996

Gnomad AMR exome AF: 0.0000526

Gnomad ASJ exome AF: 0.000293

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.000417

Gnomad NFE exome AF: 0.0000937

Gnomad OTH exome AF: 0.00

GnomAD4 exome Cov.: 31

GnomAD4 genome Data not reliable, filtered out with message: AC0;AS_VQSR AF: 0.00 AC: 0 AN: 149828 Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0 AN XY: 73180

African (AFR) AF: 0.00 AC: 0 AN: 40692

American (AMR) AF: 0.00 AC: 0 AN: 15074

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3446

East Asian (EAS) AF: 0.00 AC: 0 AN: 5016

South Asian (SAS) AF: 0.00 AC: 0 AN: 4636

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10350

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 264

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 67392

Other (OTH) AF: 0.00 AC: 0 AN: 2072

Alfa AF: 0.00155 Hom.: 0

ExAC AF: 0.0702 AC: 8514

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.15
BayesDel_addAF	Benign	-0.35	T
BayesDel_noAF	Benign	-0.74
CADD	Benign	7.1
DANN	Benign	0.91
DEOGEN2	Benign	0.059	T
Eigen	Benign	-1.0
Eigen_PC	Benign	-1.0
FATHMM_MKL	Benign	0.0014	N
LIST_S2	Benign	0.046	T
MetaRNN	Benign	0.0026	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.070	N
PhyloP100		-1.3
PrimateAI	Benign	0.29	T
PROVEAN	Benign	-2.2	N
REVEL	Benign	0.013
Sift	Benign	0.16	T
Sift4G	Benign	0.14	T
Polyphen		0.0090	B
Vest4		0.020
MutPred		0.29		Loss of phosphorylation at T327 (P = 0.0554)
MPC		0.068
ClinPred		0.014	T
GERP RS		0.23
Varity_R		0.096
gMVP		0.0088
Mutation Taster		=100/0	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: rs113884485; hg19: chr4-367206; COSMIC: COSV53656590; COSMIC: COSV53656590;