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rs769605571

chr17-72121433-G-Achr17-72121433-G-Cchr17-72121433-G-T

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_StrongBP6_ModerateBP7BS2

The NM_000346.4(SOX9):c.42G>A(p.Gln14=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000067 in 1,612,854 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.00020 ( 0 hom., cov: 31)
Exomes 𝑓: 0.000053 ( 2 hom. )

Consequence

SOX9
NM_000346.4 synonymous

Scores

1
1

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 2.04
Variant links:
Genes affected
SOX9 (HGNC:11204): (SRY-box transcription factor 9) The protein encoded by this gene recognizes the sequence CCTTGAG along with other members of the HMG-box class DNA-binding proteins. It acts during chondrocyte differentiation and, with steroidogenic factor 1, regulates transcription of the anti-Muellerian hormone (AMH) gene. Deficiencies lead to the skeletal malformation syndrome campomelic dysplasia, frequently with sex reversal. [provided by RefSeq, Jul 2008]
SOX9-AS1 (HGNC:49321): (SOX9 antisense RNA 1)

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -11 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=-0.62).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 17-72121433-G-A is Benign according to our data. Variant chr17-72121433-G-A is described in ClinVar as [Benign]. Clinvar id is 536131.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=2.04 with no splicing effect.
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 AC in GnomAd at 30 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
SOX9NM_000346.4 linkuse as main transcriptc.42G>A p.Gln14= synonymous_variant 1/3 ENST00000245479.3

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
SOX9ENST00000245479.3 linkuse as main transcriptc.42G>A p.Gln14= synonymous_variant 1/31 NM_000346.4 P1
SOX9-AS1ENST00000414600.1 linkuse as main transcriptn.96+20252C>T intron_variant, non_coding_transcript_variant 3

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.000197
AC:
30
AN:
152204
Hom.:
0
Cov.:
31
show subpopulations
Gnomad AFR
AF:
0.0000482
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00144
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:
0.0000147
Gnomad OTH
AF:
0.00239
GnomAD3 exomes
AF:
0.000162
AC:
40
AN:
246366
Hom.:
2
AF XY:
0.000134
AC XY:
18
AN XY:
134470
show subpopulations
Gnomad AFR exome
AF:
0.0000655
Gnomad AMR exome
AF:
0.000957
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:
0.0000362
Gnomad OTH exome
AF:
0.000331
GnomAD4 exome
AF:
0.0000534
AC:
78
AN:
1460650
Hom.:
2
Cov.:
31
AF XY:
0.0000495
AC XY:
36
AN XY:
726660
show subpopulations
Gnomad4 AFR exome
AF:
0.0000896
Gnomad4 AMR exome
AF:
0.00130
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000630
Gnomad4 OTH exome
AF:
0.000166
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.000197
AC:
30
AN:
152204
Hom.:
0
Cov.:
31
AF XY:
0.000188
AC XY:
14
AN XY:
74356
show subpopulations
Gnomad4 AFR
AF:
0.0000482
Gnomad4 AMR
AF:
0.00144
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000147
Gnomad4 OTH
AF:
0.00239
Alfa
AF:
0.0000516
Hom.:
0
Bravo
AF:
0.000325

ClinVar

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

Submissions by phenotype

Camptomelic dysplasia Benign:1
Benign, criteria provided, single submitterclinical testingInvitaeJan 18, 2024- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.62
Cadd
Benign
13
Dann
Uncertain
0.98
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.6

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: rs769605571; hg19: chr17-70117574; API