chr7-100057367-G-C

Variant names:

• chr7-100057367-G-C
• rs1303461267
• NM_145914.3:c.361G>C

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_145914.3(ZSCAN21):​c.361G>C​(p.Glu121Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. E121K) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: ZSCAN21 NM_145914.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.42
• Publications: 0 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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZSCAN21	NM_145914.3	c.361G>C	p.Glu121Gln	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.361G>C	p.Glu121Gln	missense_variant	Exon 2 of 4	1	NM_145914.3	ENSP00000292450.4
ZSCAN21	ENST00000456748.6	c.361G>C	p.Glu121Gln	missense_variant	Exon 2 of 5	5		ENSP00000390960.2
ZSCAN21	ENST00000438937.1	c.361G>C	p.Glu121Gln	missense_variant	Exon 3 of 4	2		ENSP00000404207.1
ZSCAN21	ENST00000477297.1	n.457G>C		non_coding_transcript_exon_variant	Exon 1 of 3	3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000756

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.35
BayesDel_addAF	Benign	-0.059	T
BayesDel_noAF	Benign	-0.32
CADD	Pathogenic	26
DANN	Uncertain	1.0
DEOGEN2	Benign	0.34	T;T;T
Eigen	Pathogenic	0.87
Eigen_PC	Pathogenic	0.75
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Benign	0.82	T;T;T
M_CAP	Benign	0.010	T
MetaRNN	Uncertain	0.46	T;T;T
MetaSVM	Benign	-0.54	T
MutationAssessor	Pathogenic	3.5	H;.;.
PhyloP100		3.4
PrimateAI	Uncertain	0.56	T
PROVEAN	Uncertain	-2.5	D;D;D
REVEL	Benign	0.21
Sift	Pathogenic	0.0	D;D;D
Sift4G	Pathogenic	0.0	D;D;D
Polyphen		1.0	D;.;.
Vest4		0.32
MutPred		0.62		Gain of helix (P = 0.0225);Gain of helix (P = 0.0225);Gain of helix (P = 0.0225);
MVP		0.68
MPC		0.55
ClinPred		0.99	D
GERP RS		4.8
Varity_R		0.48
gMVP		0.46
Mutation Taster		=79/21	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: rs1303461267; hg19: chr7-99654990; COSMIC: COSV52851445;