Genetic Variant NM_001257096.2:c.18C>A (chr20-21705730-C-A) – ACMG Classification: Likely_benign (-3 pts)

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2BP4_ModerateBP6_ModerateBP7

The NM_001257096.2(PAX1):c.18C>A(p.Gly6Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000182 in 1,097,086 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000018 ( 0 hom. )

Consequence

PAX1
NM_001257096.2 synonymous

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 2.76

Variant links:

Genes affected

PAX1 (HGNC:8615): (paired box 1) This gene is a member of the paired box (PAX) family of transcription factors. Members of the PAX family typically contain a paired box domain and a paired-type homeodomain. These genes play critical roles during fetal development. This gene plays a role in pattern formation during embryogenesis and may be essential for development of the vertebral column. This gene is silenced by methylation in ovarian and cervical cancers and may be a tumor suppressor gene. Mutations in this gene are also associated with vertebral malformations. [provided by RefSeq, Mar 2012]

PAX1 links:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.39).

BP6

Variant 20-21705730-C-A is Benign according to our data. Variant chr20-21705730-C-A is described in ClinVar as [Likely_benign]. Clinvar id is 2003620.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=2.76 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PAX1	NM_001257096.2 link	c.18C>A	p.Gly6Gly	synonymous_variant	Exon 1 of 5	ENST00000613128.5	NP_001244025.1	A0A087WXV5
PAX1	NM_006192.5 link	c.18C>A	p.Gly6Gly	synonymous_variant	Exon 1 of 5		NP_006183.2	P15863-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PAX1	ENST00000613128.5 link	c.18C>A	p.Gly6Gly	synonymous_variant	Exon 1 of 5	1	NM_001257096.2	ENSP00000481334.1		A0A087WXV5
PAX1	ENST00000398485.6 link	c.18C>A	p.Gly6Gly	synonymous_variant	Exon 1 of 5	5		ENSP00000381499.2		P15863-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000182

AC:

AN:

1097086

Hom.:

Cov.:

AF XY:

0.00000385

AC XY:

AN XY:

520010

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

22808

American (AMR)

AF:

0.00

AC:

AN:

8242

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

14152

East Asian (EAS)

AF:

0.00

AC:

AN:

26460

South Asian (SAS)

AF:

0.0000507

AC:

AN:

19712

European-Finnish (FIN)

AF:

0.00

AC:

AN:

35494

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3608

European-Non Finnish (NFE)

AF:

0.00000108

AC:

AN:

922928

Other (OTH)

AF:

0.00

AC:

AN:

43682

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

GnomAD4 genome

Cov.:

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Feb 17, 2024

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.39

CADD

Benign

9.5

(source)

DANN

Benign

0.89

PhyloP100

2.8

PromoterAI

-0.055

Neutral

(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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NM_001257096.2:c.18C>A

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over