chr7-100057066-G-T

Position:

• chr7-100057066-G-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_145914.3(ZSCAN21):​c.60G>T​(p.Gln20His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,826 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 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: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: ZSCAN21 NM_145914.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.403

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]

ZSCAN21 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.15299293).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZSCAN21	NM_145914.3	c.60G>T	p.Gln20His	missense_variant	2/4	ENST00000292450.9	NP_666019.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZSCAN21	ENST00000292450.9	c.60G>T	p.Gln20His	missense_variant	2/4	1	NM_145914.3	ENSP00000292450.4
ZSCAN21	ENST00000456748.6	c.60G>T	p.Gln20His	missense_variant	2/5	5		ENSP00000390960.2
ZSCAN21	ENST00000438937.1	c.60G>T	p.Gln20His	missense_variant	3/4	2		ENSP00000404207.1
ZSCAN21	ENST00000477297.1	n.156G>T		non_coding_transcript_exon_variant	1/3	3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461826 Hom.: 0 Cov.: 36 AF XY: 0.00000138 AC XY: 1 AN XY: 727210

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000116

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.17
BayesDel_addAF	Benign	-0.23	T
BayesDel_noAF	Benign	-0.57
CADD	Benign	14
DANN	Uncertain	0.99
DEOGEN2	Uncertain	0.47	T;T;T;T
Eigen	Benign	-0.051
Eigen_PC	Benign	-0.051
FATHMM_MKL	Benign	0.44	N
LIST_S2	Benign	0.21	T;T;T;T
M_CAP	Benign	0.0031	T
MetaRNN	Benign	0.15	T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.3	M;.;.;.
PrimateAI	Benign	0.38	T
PROVEAN	Uncertain	-2.7	D;D;D;D
REVEL	Benign	0.075
Sift	Uncertain	0.012	D;D;D;D
Sift4G	Uncertain	0.012	D;D;D;D
Polyphen		0.41	B;.;.;D
Vest4		0.15
MutPred		0.26		Loss of sheet (P = 0.0104);Loss of sheet (P = 0.0104);Loss of sheet (P = 0.0104);Loss of sheet (P = 0.0104);
MVP		0.66
MPC		0.23
ClinPred		0.60	D
GERP RS		4.0
Varity_R		0.16
gMVP		0.45

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: rs11558476; hg19: chr7-99654689;