7-99622554-C-T

Variant names:

• chr7-99622554-C-T
• rs137966152
• NM_145115.3:c.595C>T

Variant summary

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

The NM_145115.3(ZSCAN25):​c.595C>T​(p.Pro199Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000707 in 1,614,168 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/24 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00039 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00074 (0 hom.)
• Consequence: ZSCAN25 NM_145115.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.54
• Publications: 6 publications found

Genes affected

ZSCAN25 (HGNC:21961): (zinc finger and SCAN domain containing 25) This gene encodes a protein that bears some similarity to zinc finger proteins, which are involved in DNA binding and protein-protein interactions. Multiple alternatively spliced transcript variants have been identified, but the full-length nature for most of them has not been determined. [provided by RefSeq, Jul 2008]

ACMG classification

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZSCAN25	NM_145115.3	c.595C>T	p.Pro199Ser	missense_variant	Exon 6 of 8	ENST00000394152.7	NP_660090.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZSCAN25	ENST00000394152.7	c.595C>T	p.Pro199Ser	missense_variant	Exon 6 of 8	5	NM_145115.3	ENSP00000377708.2

Frequencies

GnomAD3 genomes AF: 0.000388 AC: 59 AN: 152194 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000241

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000654

Gnomad ASJ AF: 0.000288

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.0000942

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000794

Gnomad OTH AF: 0.000478

GnomAD2 exomes AF: 0.000493 AC: 124 AN: 251410 AF XY: 0.000449

Gnomad AFR exome AF: 0.0000615

Gnomad AMR exome AF: 0.000347

Gnomad ASJ exome AF: 0.000595

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.000416

Gnomad NFE exome AF: 0.000827

Gnomad OTH exome AF: 0.000326

GnomAD4 exome AF: 0.000740 AC: 1082 AN: 1461856 Hom.: 0 Cov.: 30 AF XY: 0.000715 AC XY: 520 AN XY: 727230

African (AFR) AF: 0.0000299 AC: 1 AN: 33478

American (AMR) AF: 0.000313 AC: 14 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.000459 AC: 12 AN: 26134

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

South Asian (SAS) AF: 0.0000464 AC: 4 AN: 86258

European-Finnish (FIN) AF: 0.000487 AC: 26 AN: 53416

Middle Eastern (MID) AF: 0.000173 AC: 1 AN: 5768

European-Non Finnish (NFE) AF: 0.000888 AC: 987 AN: 1111982

Other (OTH) AF: 0.000613 AC: 37 AN: 60396

GnomAD4 genome AF: 0.000387 AC: 59 AN: 152312 Hom.: 0 Cov.: 32 AF XY: 0.000363 AC XY: 27 AN XY: 74470

African (AFR) AF: 0.0000241 AC: 1 AN: 41566

American (AMR) AF: 0.0000654 AC: 1 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.000288 AC: 1 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5182

South Asian (SAS) AF: 0.00 AC: 0 AN: 4830

European-Finnish (FIN) AF: 0.0000942 AC: 1 AN: 10612

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000794 AC: 54 AN: 68032

Other (OTH) AF: 0.000473 AC: 1 AN: 2112

Alfa AF: 0.000792 Hom.: 0

Bravo AF: 0.000457

TwinsUK AF: 0.00135 AC: 5

ALSPAC AF: 0.000259 AC: 1

ESP6500AA AF: 0.000227 AC: 1

ESP6500EA AF: 0.00151 AC: 13

ExAC AF: 0.000560 AC: 68

EpiCase AF: 0.00120

EpiControl AF: 0.000593

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Aug 12, 2021

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.595C>T (p.P199S) alteration is located in exon 6 (coding exon 3) of the ZSCAN25 gene. This alteration results from a C to T substitution at nucleotide position 595, causing the proline (P) at amino acid position 199 to be replaced by a serine (S). 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	-0.55	T
BayesDel_noAF	Benign	-0.60
CADD	Benign	19
DANN	Benign	0.58
DEOGEN2	Benign	0.062	T;T
Eigen	Benign	-0.59
Eigen_PC	Benign	-0.51
FATHMM_MKL	Benign	0.72	D
LIST_S2	Benign	0.70	.;T
M_CAP	Benign	0.0058	T
MetaRNN	Benign	0.021	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.0	L;L
PhyloP100		1.5
PrimateAI	Benign	0.45	T
PROVEAN	Uncertain	-3.0	D;D
REVEL	Benign	0.045
Sift	Benign	0.18	T;T
Sift4G	Benign	0.20	T;T
Polyphen		0.011	B;B
Vest4		0.27
MVP		0.14
MPC		0.27
ClinPred		0.016	T
GERP RS		4.0
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.050
gMVP		0.27
Mutation Taster		=96/4	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.33		Details are displayed if max score is > 0.2
DS_AG_spliceai		0.33		Position offset: 12

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs137966152; hg19: chr7-99220177; COSMIC: COSV53552609; COSMIC: COSV53552609;