rs10141867

Variant names:

• chr14-104801767-G-A
• rs10141867
• NM_001137601.3:c.570G>A

Your query was ambiguous. Multiple possible variants found:

• chr14-104801767-G-A
• chr14-104801767-G-C

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001137601.3(ZBTB42):​c.570G>A​(p.Leu190Leu) variant causes a synonymous change. The variant allele was found at a frequency of 0.274 in 1,548,706 control chromosomes in the GnomAD database, including 59,318 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.28 (6127 hom., cov: 34)
  • Exomes 𝑓: 0.27 (53191 hom.)
• Consequence: ZBTB42 NM_001137601.3 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 4.02
• Publications: 19 publications found

Genes affected

ZBTB42 (HGNC:32550): (zinc finger and BTB domain containing 42) The protein encoded by this gene is a member of the C2H2 zinc finger protein family. This protein is predicted to have a pox virus and zinc finger (POZ) domain at the N-terminus and four zinc finger domains at the C-terminus. In human and mouse, the protein localizes to the nuclei of skeletal muscle cells. Knockdown of this gene in zebrafish results in abnormal skeletal muscle development and myofibrillar disorganization. A novel homozygous variant of the human gene has been associated with lethal congenital contracture syndrome, an autosomal recessive disorder that results in muscle wasting. [provided by RefSeq, Mar 2015]

ZBTB42 Gene-Disease associations (from GenCC):

• lethal congenital contracture syndrome 6

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

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.59).
• BP6: Variant 14-104801767-G-A is Benign according to our data. Variant chr14-104801767-G-A is described in ClinVar as Benign. ClinVar VariationId is 1260467.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.307 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001137601.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZBTB42	NM_001137601.3	MANE Select	c.570G>A	p.Leu190Leu	synonymous	Exon 1 of 1	NP_001131073.1
	ZBTB42	NM_001370342.1		c.570G>A	p.Leu190Leu	synonymous	Exon 2 of 2	NP_001357271.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZBTB42	ENST00000342537.8	TSL:6 MANE Select	c.570G>A	p.Leu190Leu	synonymous	Exon 1 of 1	ENSP00000409107.2
	ZBTB42	ENST00000555360.1	TSL:1	c.570G>A	p.Leu190Leu	synonymous	Exon 2 of 2	ENSP00000450673.1

Frequencies

GnomAD3 genomes AF: 0.277 AC: 42125 AN: 152046 Hom.: 6116 Cov.: 34

Gnomad AFR AF: 0.311

Gnomad AMI AF: 0.273

Gnomad AMR AF: 0.236

Gnomad ASJ AF: 0.252

Gnomad EAS AF: 0.106

Gnomad SAS AF: 0.175

Gnomad FIN AF: 0.292

Gnomad MID AF: 0.165

Gnomad NFE AF: 0.286

Gnomad OTH AF: 0.265

GnomAD2 exomes AF: 0.242 AC: 36710 AN: 151526 AF XY: 0.242

Gnomad AFR exome AF: 0.320

Gnomad AMR exome AF: 0.197

Gnomad ASJ exome AF: 0.229

Gnomad EAS exome AF: 0.113

Gnomad FIN exome AF: 0.293

Gnomad NFE exome AF: 0.282

Gnomad OTH exome AF: 0.257

GnomAD4 exome AF: 0.274 AC: 382272 AN: 1396542 Hom.: 53191 Cov.: 86 AF XY: 0.271 AC XY: 186906 AN XY: 688572

African (AFR) AF: 0.316 AC: 9964 AN: 31568

American (AMR) AF: 0.208 AC: 7416 AN: 35588

Ashkenazi Jewish (ASJ) AF: 0.235 AC: 5895 AN: 25132

East Asian (EAS) AF: 0.138 AC: 4944 AN: 35714

South Asian (SAS) AF: 0.194 AC: 15354 AN: 79068

European-Finnish (FIN) AF: 0.292 AC: 13991 AN: 47848

Middle Eastern (MID) AF: 0.186 AC: 1056 AN: 5688

European-Non Finnish (NFE) AF: 0.286 AC: 308660 AN: 1078046

Other (OTH) AF: 0.259 AC: 14992 AN: 57890

GnomAD4 genome AF: 0.277 AC: 42172 AN: 152164 Hom.: 6127 Cov.: 34 AF XY: 0.275 AC XY: 20428 AN XY: 74388

African (AFR) AF: 0.311 AC: 12917 AN: 41504

American (AMR) AF: 0.236 AC: 3603 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.252 AC: 874 AN: 3472

East Asian (EAS) AF: 0.107 AC: 552 AN: 5180

South Asian (SAS) AF: 0.176 AC: 850 AN: 4822

European-Finnish (FIN) AF: 0.292 AC: 3091 AN: 10594

Middle Eastern (MID) AF: 0.173 AC: 51 AN: 294

European-Non Finnish (NFE) AF: 0.286 AC: 19424 AN: 67984

Other (OTH) AF: 0.266 AC: 562 AN: 2112

Alfa AF: 0.255 Hom.: 2938

Bravo AF: 0.276

Asia WGS AF: 0.135 AC: 466 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.59
CADD	Benign	9.5
DANN	Benign	0.81
PhyloP100		4.0
Mutation Taster		=96/4	polymorphism (auto)

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: rs10141867; hg19: chr14-105268104; COSMIC: COSV61137453;