Genetic Variant NM_001322064.3:c.974C>G (chr19-56222092-G-C) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001322064.3(ZSCAN5A):c.974C>G(p.Pro325Arg) 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 1,461,696 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/22 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. P325L) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

ZSCAN5A
NM_001322064.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.515

Publications

0 publications found

Variant links:

Genes affected

ZSCAN5A (HGNC:23710): (zinc finger and SCAN domain containing 5A) Enables sequence-specific double-stranded DNA binding activity. Predicted to be involved in regulation of transcription by RNA polymerase II. Predicted to be located in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ZSCAN5A links:

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ACMG classification

Classification was made for transcript

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=0.1441037).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001322064.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ZSCAN5A	NM_001322064.3	MANE Select	c.974C>G	p.Pro325Arg	missense	Exon 6 of 6	NP_001308993.1	Q9BUG6-1
ZSCAN5A	NM_001322065.3		c.974C>G	p.Pro325Arg	missense	Exon 6 of 6	NP_001308994.1	Q9BUG6-1
ZSCAN5A	NM_001322066.2		c.974C>G	p.Pro325Arg	missense	Exon 6 of 6	NP_001308995.1	Q9BUG6-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ZSCAN5A	ENST00000683990.1	MANE Select	c.974C>G	p.Pro325Arg	missense	Exon 6 of 6	ENSP00000507065.1	Q9BUG6-1
ZSCAN5A	ENST00000391713.5	TSL:1	c.974C>G	p.Pro325Arg	missense	Exon 5 of 5	ENSP00000375593.1	Q9BUG6-1
ZSCAN5A	ENST00000587340.5	TSL:1	c.974C>G	p.Pro325Arg	missense	Exon 7 of 7	ENSP00000467631.1	Q9BUG6-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461696

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

727150

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33480

American (AMR)

AF:

0.00

AC:

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26134

East Asian (EAS)

AF:

0.0000252

AC:

AN:

39700

South Asian (SAS)

AF:

0.00

AC:

AN:

86258

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53414

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1111824

Other (OTH)

AF:

0.00

AC:

AN:

60394

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.14

BayesDel_addAF

Benign

-0.32

BayesDel_noAF

Benign

-0.70

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.021

Eigen

Benign

-0.34

Eigen_PC

Benign

-0.63

FATHMM_MKL

Benign

0.026

LIST_S2

Benign

0.57

M_CAP

Benign

0.0031

MetaRNN

Benign

0.14

MetaSVM

Benign

-1.0

MutationAssessor

Uncertain

2.1

PhyloP100

0.52

PrimateAI

Benign

0.22

PROVEAN

Uncertain

-2.5

REVEL

Benign

0.025

Sift

Benign

0.20

Sift4G

Benign

0.13

Polyphen

0.95

Vest4

0.054

MutPred

0.37

Gain of MoRF binding (P = 0.0141)

MVP

0.33

MPC

0.29

ClinPred

0.44

GERP RS

0.85

Varity_R

0.037

gMVP

0.16

Mutation Taster

=99/1

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over