NM_001023560.4:c.1124C>G

Variant names:

• chr6-28276780-C-G
• rs1361968542
• NM_001023560.4:c.1124C>G

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001023560.4(ZSCAN26):​c.1124C>G​(p.Thr375Ser) 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 1,461,688 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 8/12 in silico tools predict a benign outcome for this variant. 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. T375N) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: ZSCAN26 NM_001023560.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.552
• Publications: 0 publications found

Genes affected

ZSCAN26 (HGNC:12978): (zinc finger and SCAN domain containing 26) Predicted to enable DNA-binding transcription factor activity, RNA polymerase II-specific and RNA polymerase II cis-regulatory region sequence-specific DNA binding activity. Predicted to be involved in regulation of transcription by RNA polymerase II. Located in cytosol and nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

ENSG00000276302 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.07753098).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001023560.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZSCAN26	NM_001023560.4	MANE Select	c.1124C>G	p.Thr375Ser	missense	Exon 4 of 4	NP_001018854.2	A0A024RCN4
	ZSCAN26	NM_001111039.3		c.1121C>G	p.Thr374Ser	missense	Exon 4 of 4	NP_001104509.1	Q16670-1
	ZSCAN26	NM_001287421.2		c.719C>G	p.Thr240Ser	missense	Exon 4 of 4	NP_001274350.1	A0A087X2F1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZSCAN26	ENST00000421553.7	TSL:1 MANE Select	c.1124C>G	p.Thr375Ser	missense	Exon 4 of 4	ENSP00000481707.1	A0A024RCN4
	ZSCAN26	ENST00000316606.10	TSL:1	c.719C>G	p.Thr240Ser	missense	Exon 4 of 4	ENSP00000484931.1	A0A087X2F1
	ENSG00000276302	ENST00000621053.1	TSL:4	c.133+3993C>G		intron	N/A	ENSP00000481142.1	A0A087WXM4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00000401 AC: 1 AN: 249096 AF XY: 0.00000740

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.000166

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461688 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 727124

African (AFR) AF: 0.00 AC: 0 AN: 33478

American (AMR) AF: 0.00 AC: 0 AN: 44720

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26132

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86256

European-Finnish (FIN) AF: 0.0000187 AC: 1 AN: 53400

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1111862

Other (OTH) AF: 0.00 AC: 0 AN: 60372

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.15
BayesDel_addAF	Uncertain	0.088	D
BayesDel_noAF	Benign	-0.11
CADD	Benign	15
DANN	Benign	0.74
DEOGEN2	Benign	0.0030	T
FATHMM_MKL	Benign	0.029	N
LIST_S2	Benign	0.20	T
MetaRNN	Benign	0.078	T
PhyloP100		0.55
PrimateAI	Benign	0.41	T
Sift4G	Benign	0.25	T
Polyphen		0.23	B
Vest4		0.057
MVP		0.32
GERP RS		3.2
Varity_R		0.056
gMVP		0.029

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: rs1361968542; hg19: chr6-28244557; COSMIC: COSV52554651; COSMIC: COSV52554651;