rs138713462

Variant names:

• chr7-100057085-A-G
• rs138713462
• NM_145914.3:c.79A>G

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM1 BP4_Moderate

The NM_145914.3(ZSCAN21):​c.79A>G​(p.Lys27Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000643 in 1,613,950 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00026 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00068 (0 hom.)
• Consequence: ZSCAN21 NM_145914.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.97
• Publications: 2 publications found

Genes affected

ZSCAN21 (HGNC:13104): (zinc finger and SCAN domain containing 21) Enables DNA-binding transcription activator activity, RNA polymerase II-specific and RNA polymerase II cis-regulatory region sequence-specific DNA binding activity. Involved in positive 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: Uncertain_significance. The variant received 0 ACMG points.

• PM1: In a cross_link Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2) (size 0) in uniprot entity ZSC21_HUMAN
• BP4: Computational evidence support a benign effect (MetaRNN=0.07285464).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZSCAN21	NM_145914.3	c.79A>G	p.Lys27Glu	missense_variant	Exon 2 of 4	ENST00000292450.9	NP_666019.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZSCAN21	ENST00000292450.9	c.79A>G	p.Lys27Glu	missense_variant	Exon 2 of 4	1	NM_145914.3	ENSP00000292450.4
ZSCAN21	ENST00000456748.6	c.79A>G	p.Lys27Glu	missense_variant	Exon 2 of 5	5		ENSP00000390960.2
ZSCAN21	ENST00000438937.1	c.79A>G	p.Lys27Glu	missense_variant	Exon 3 of 4	2		ENSP00000404207.1
ZSCAN21	ENST00000477297.1	n.175A>G		non_coding_transcript_exon_variant	Exon 1 of 3	3

Frequencies

GnomAD3 genomes AF: 0.000263 AC: 40 AN: 152112 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000121

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000655

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: 0.000500

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000278 AC: 70 AN: 251446 AF XY: 0.000265

Gnomad AFR exome AF: 0.000369

Gnomad AMR exome AF: 0.000463

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000422

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.000682 AC: 997 AN: 1461838 Hom.: 0 Cov.: 32 AF XY: 0.000678 AC XY: 493 AN XY: 727218

African (AFR) AF: 0.000209 AC: 7 AN: 33480

American (AMR) AF: 0.000403 AC: 18 AN: 44720

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39698

South Asian (SAS) AF: 0.00 AC: 0 AN: 86252

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53410

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5760

European-Non Finnish (NFE) AF: 0.000841 AC: 935 AN: 1111988

Other (OTH) AF: 0.000613 AC: 37 AN: 60394

GnomAD4 genome AF: 0.000263 AC: 40 AN: 152112 Hom.: 0 Cov.: 32 AF XY: 0.000202 AC XY: 15 AN XY: 74302

African (AFR) AF: 0.000121 AC: 5 AN: 41418

American (AMR) AF: 0.0000655 AC: 1 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5186

South Asian (SAS) AF: 0.00 AC: 0 AN: 4820

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10622

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.000500 AC: 34 AN: 68018

Other (OTH) AF: 0.00 AC: 0 AN: 2088

Alfa AF: 0.000510 Hom.: 0

Bravo AF: 0.000359

TwinsUK AF: 0.000539 AC: 2

ALSPAC AF: 0.000259 AC: 1

ESP6500AA AF: 0.000454 AC: 2

ESP6500EA AF: 0.000349 AC: 3

ExAC AF: 0.000222 AC: 27

EpiCase AF: 0.000491

EpiControl AF: 0.000533

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Feb 20, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.79A>G (p.K27E) alteration is located in exon 2 (coding exon 1) of the ZSCAN21 gene. This alteration results from a A to G substitution at nucleotide position 79, causing the lysine (K) at amino acid position 27 to be replaced by a glutamic acid (E). 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	0.11
BayesDel_addAF	Benign	-0.29	T
BayesDel_noAF	Benign	-0.34
CADD	Benign	21
DANN	Uncertain	0.98
DEOGEN2	Uncertain	0.52	D;T;T;T
Eigen	Benign	-0.16
Eigen_PC	Benign	-0.24
FATHMM_MKL	Benign	0.16	N
LIST_S2	Benign	0.79	T;T;T;T
M_CAP	Benign	0.0048	T
MetaRNN	Benign	0.073	T;T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.3	M;.;.;.
PhyloP100		2.0
PrimateAI	Uncertain	0.56	T
PROVEAN	Uncertain	-2.5	D;D;D;D
REVEL	Benign	0.15
Sift	Uncertain	0.018	D;D;D;D
Sift4G	Uncertain	0.045	D;D;T;T
Polyphen		0.99	D;.;.;P
Vest4		0.31
MVP		0.25
MPC		0.26
ClinPred		0.076	T
GERP RS		4.6
Varity_R		0.20
gMVP		0.65
Mutation Taster		=99/1	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: rs138713462; hg19: chr7-99654708;