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GeneBe

1-37483335-C-T

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_StrongBP6_ModerateBP7BS1BS2

The NM_025079.3(ZC3H12A):c.1524C>T(p.Ala508=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000971 in 1,614,162 control chromosomes in the GnomAD database, including 19 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0052 ( 8 hom., cov: 33)
Exomes 𝑓: 0.00053 ( 11 hom. )

Consequence

ZC3H12A
NM_025079.3 synonymous

Scores

2

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.753
Variant links:
Genes affected
ZC3H12A (HGNC:26259): (zinc finger CCCH-type containing 12A) ZC3H12A is an MCP1 (CCL2; MIM 158105)-induced protein that acts as a transcriptional activator and causes cell death of cardiomyocytes, possibly via induction of genes associated with apoptosis.[supplied by OMIM, Mar 2008]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -15 ACMG points.

BP4
?
    BP4 - Multiple lines of computational evidence suggest no impact on gene or gene product (conservation, evolutionary, splicing impact, etc.)
Computational evidence support a benign effect (BayesDel_noAF=-0.78).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 1-37483335-C-T is Benign according to our data. Variant chr1-37483335-C-T is described in ClinVar as [Benign]. Clinvar id is 784946.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
?
    BP7 - A synonymous (silent) variant for which splicing prediction algorithms predict no impact to the splice consensus sequence nor the creation of a new splice site AND the nucleotide is not highly conserved
Synonymous conserved (PhyloP=-0.753 with no splicing effect.
BS1
?
    BS1 - Allele frequency is greater than expected for disorder
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00519 (791/152316) while in subpopulation AFR AF= 0.0182 (755/41572). AF 95% confidence interval is 0.0171. There are 8 homozygotes in gnomad4. There are 375 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
BS2
?
    BS2 - Observed in a healthy adult individual for a recessive (homozygous), dominant (heterozygous), or X-linked (hemizygous) disorder, with full penetrance expected at an early age
High Homozygotes in GnomAd at 8 AR gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
ZC3H12ANM_025079.3 linkuse as main transcriptc.1524C>T p.Ala508= synonymous_variant 6/6 ENST00000373087.7

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
ZC3H12AENST00000373087.7 linkuse as main transcriptc.1524C>T p.Ala508= synonymous_variant 6/61 NM_025079.3 P1
ZC3H12AENST00000640233.1 linkuse as main transcriptc.*756C>T 3_prime_UTR_variant, NMD_transcript_variant 6/65

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00518
AC:
789
AN:
152198
Hom.:
8
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.0182
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00183
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000294
Gnomad OTH
AF:
0.00287
GnomAD3 exomes
AF:
0.00126
AC:
316
AN:
251338
Hom.:
1
AF XY:
0.000898
AC XY:
122
AN XY:
135882
show subpopulations
Gnomad AFR exome
AF:
0.0171
Gnomad AMR exome
AF:
0.000896
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000264
Gnomad OTH exome
AF:
0.000815
GnomAD4 exome
AF:
0.000531
AC:
776
AN:
1461846
Hom.:
11
Cov.:
32
AF XY:
0.000440
AC XY:
320
AN XY:
727230
show subpopulations
Gnomad4 AFR exome
AF:
0.0190
Gnomad4 AMR exome
AF:
0.00105
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000464
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000899
Gnomad4 OTH exome
AF:
0.00129
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00519
AC:
791
AN:
152316
Hom.:
8
Cov.:
33
AF XY:
0.00504
AC XY:
375
AN XY:
74478
show subpopulations
Gnomad4 AFR
AF:
0.0182
Gnomad4 AMR
AF:
0.00183
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000294
Gnomad4 OTH
AF:
0.00284
Alfa
AF:
0.00255
Hom.:
0
Bravo
AF:
0.00627

ClinVar

Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not provided Benign:1
Benign, criteria provided, single submitterclinical testingInvitaeJun 21, 2018- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.78
Cadd
Benign
3.7
Dann
Benign
0.52

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

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs149154302; hg19: chr1-37948936; API