15-43366737-C-T

Variant names:

• chr15-43366737-C-T
• rs3917221
• NM_001372080.1:c.595G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001372080.1(ZSCAN29):​c.595G>A​(p.Gly199Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.182 in 1,614,042 control chromosomes in the GnomAD database, including 28,574 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.17 (2444 hom., cov: 32)
  • Exomes 𝑓: 0.18 (26130 hom.)
• Consequence: ZSCAN29 NM_001372080.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.485
• Publications: 26 publications found

Genes affected

ZSCAN29 (HGNC:26673): (zinc finger and SCAN domain containing 29) Enables sequence-specific double-stranded DNA binding activity. Predicted to be involved in regulation of transcription by RNA polymerase II. Predicted to be located in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0012399852).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.185 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZSCAN29	NM_001372080.1	c.595G>A	p.Gly199Ser	missense_variant	Exon 4 of 6	ENST00000684362.1	NP_001359009.1
ZSCAN29	NM_152455.4	c.595G>A	p.Gly199Ser	missense_variant	Exon 3 of 5		NP_689668.3
ZSCAN29	XM_047432187.1	c.595G>A	p.Gly199Ser	missense_variant	Exon 4 of 6		XP_047288143.1
ZSCAN29	XM_047432188.1	c.-384G>A		5_prime_UTR_variant	Exon 2 of 4		XP_047288144.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZSCAN29	ENST00000684362.1	c.595G>A	p.Gly199Ser	missense_variant	Exon 4 of 6		NM_001372080.1	ENSP00000507363.1

Frequencies

GnomAD3 genomes AF: 0.172 AC: 26196 AN: 152058 Hom.: 2446 Cov.: 32

Gnomad AFR AF: 0.187

Gnomad AMI AF: 0.117

Gnomad AMR AF: 0.142

Gnomad ASJ AF: 0.212

Gnomad EAS AF: 0.00135

Gnomad SAS AF: 0.191

Gnomad FIN AF: 0.121

Gnomad MID AF: 0.272

Gnomad NFE AF: 0.188

Gnomad OTH AF: 0.186

GnomAD2 exomes AF: 0.161 AC: 40472 AN: 251432 AF XY: 0.167

Gnomad AFR exome AF: 0.186

Gnomad AMR exome AF: 0.101

Gnomad ASJ exome AF: 0.206

Gnomad EAS exome AF: 0.00250

Gnomad FIN exome AF: 0.126

Gnomad NFE exome AF: 0.189

Gnomad OTH exome AF: 0.178

GnomAD4 exome AF: 0.183 AC: 267372 AN: 1461866 Hom.: 26130 Cov.: 33 AF XY: 0.185 AC XY: 134225 AN XY: 727234

African (AFR) AF: 0.187 AC: 6257 AN: 33480

American (AMR) AF: 0.106 AC: 4729 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.208 AC: 5428 AN: 26136

East Asian (EAS) AF: 0.00149 AC: 59 AN: 39700

South Asian (SAS) AF: 0.219 AC: 18918 AN: 86254

European-Finnish (FIN) AF: 0.128 AC: 6842 AN: 53416

Middle Eastern (MID) AF: 0.257 AC: 1484 AN: 5768

European-Non Finnish (NFE) AF: 0.191 AC: 212712 AN: 1111994

Other (OTH) AF: 0.181 AC: 10943 AN: 60394

GnomAD4 genome AF: 0.172 AC: 26207 AN: 152176 Hom.: 2444 Cov.: 32 AF XY: 0.168 AC XY: 12496 AN XY: 74394

African (AFR) AF: 0.187 AC: 7769 AN: 41502

American (AMR) AF: 0.142 AC: 2165 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.212 AC: 736 AN: 3472

East Asian (EAS) AF: 0.00135 AC: 7 AN: 5180

South Asian (SAS) AF: 0.190 AC: 916 AN: 4816

European-Finnish (FIN) AF: 0.121 AC: 1279 AN: 10608

Middle Eastern (MID) AF: 0.272 AC: 80 AN: 294

European-Non Finnish (NFE) AF: 0.188 AC: 12760 AN: 67984

Other (OTH) AF: 0.184 AC: 388 AN: 2112

Alfa AF: 0.184 Hom.: 7972

Bravo AF: 0.173

TwinsUK AF: 0.194 AC: 719

ALSPAC AF: 0.187 AC: 721

ESP6500AA AF: 0.192 AC: 845

ESP6500EA AF: 0.189 AC: 1622

ExAC AF: 0.165 AC: 20029

Asia WGS AF: 0.0880 AC: 310 AN: 3478

EpiCase AF: 0.194

EpiControl AF: 0.192

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.10
BayesDel_addAF	Benign	-0.73	T
BayesDel_noAF	Benign	-0.67
CADD	Benign	14
DANN	Uncertain	0.99
DEOGEN2	Benign	0.0097	T;.;T;T
Eigen	Benign	-0.65
Eigen_PC	Benign	-0.53
FATHMM_MKL	Benign	0.17	N
LIST_S2	Benign	0.68	T;T;T;T
MetaRNN	Benign	0.0012	T;T;T;T
MetaSVM	Benign	-0.92	T
MutationAssessor	Benign	0.95	L;.;.;.
PhyloP100		0.48
PrimateAI	Benign	0.27	T
PROVEAN	Benign	-0.59	N;.;N;N
REVEL	Benign	0.046
Sift	Benign	0.57	T;.;T;T
Sift4G	Benign	0.59	T;T;T;T
Polyphen		0.0060	B;.;B;.
Vest4		0.096
MPC		0.094
ClinPred		0.0031	T
GERP RS		3.2
Varity_R		0.020
gMVP		0.16
Mutation Taster		=96/4	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		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: rs3917221; hg19: chr15-43658935; COSMIC: COSV53019147; COSMIC: COSV53019147;