6-32041801-G-A

Variant names:

• chr6-32041801-G-A
• rs1203694843
• NM_001365276.2:c.12603C>T

Variant summary

Our verdict is Benign. The variant received -7 ACMG points: 0P and 7B. BP4_Strong BP6_Moderate BP7

The NM_001365276.2(TNXB):​c.12603C>T​(p.Asn4201Asn) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0000078 (0 hom., cov: 18)
  • Exomes 𝑓: 0.000022 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: TNXB NM_001365276.2 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -2.90
• Publications: 1 publications found

Genes affected

TNXB (HGNC:11976): (tenascin XB) This gene encodes a member of the tenascin family of extracellular matrix glycoproteins. The tenascins have anti-adhesive effects, as opposed to fibronectin which is adhesive. This protein is thought to function in matrix maturation during wound healing, and its deficiency has been associated with the connective tissue disorder Ehlers-Danlos syndrome. This gene localizes to the major histocompatibility complex (MHC) class III region on chromosome 6. It is one of four genes in this cluster which have been duplicated. The duplicated copy of this gene is incomplete and is a pseudogene which is transcribed but does not encode a protein. The structure of this gene is unusual in that it overlaps the CREBL1 and CYP21A2 genes at its 5' and 3' ends, respectively. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

CYP21A2 (HGNC:2600): (cytochrome P450 family 21 subfamily A member 2) This gene encodes a member of the cytochrome P450 superfamily of enzymes. The cytochrome P450 proteins are monooxygenases which catalyze many reactions involved in drug metabolism and synthesis of cholesterol, steroids and other lipids. This protein localizes to the endoplasmic reticulum and hydroxylates steroids at the 21 position. Its activity is required for the synthesis of steroid hormones including cortisol and aldosterone. Mutations in this gene cause congenital adrenal hyperplasia. A related pseudogene is located near this gene; gene conversion events involving the functional gene and the pseudogene are thought to account for many cases of steroid 21-hydroxylase deficiency. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

CYP21A2 Gene-Disease associations (from GenCC):

• classic congenital adrenal hyperplasia due to 21-hydroxylase deficiency

  Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), Myriad Women’s Health, Laboratory for Molecular Medicine
• classic congenital adrenal hyperplasia due to 21-hydroxylase deficiency, salt wasting form

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
• classic congenital adrenal hyperplasia due to 21-hydroxylase deficiency, simple virilizing form

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -7 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.57).
• BP6: Variant 6-32041801-G-A is Benign according to our data. Variant chr6-32041801-G-A is described in ClinVar as Likely_benign. ClinVar VariationId is 1711621.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-2.9 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001365276.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TNXB	NM_001365276.2	MANE Select	c.12603C>T	p.Asn4201Asn	synonymous	Exon 43 of 44	NP_001352205.1	P22105-3
	TNXB	NM_001428335.1		c.13344C>T	p.Asn4448Asn	synonymous	Exon 44 of 45	NP_001415264.1	A0A3B3ISX9
	TNXB	NM_019105.8		c.12597C>T	p.Asn4199Asn	synonymous	Exon 43 of 44	NP_061978.6

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TNXB	ENST00000644971.2	MANE Select	c.12603C>T	p.Asn4201Asn	synonymous	Exon 43 of 44	ENSP00000496448.1	P22105-3
	TNXB	ENST00000451343.4	TSL:1	c.1890C>T	p.Asn630Asn	synonymous	Exon 12 of 13	ENSP00000407685.1	P22105-2
	TNXB	ENST00000490077.5	TSL:1	n.2430C>T		non_coding_transcript_exon	Exon 13 of 14

Frequencies

GnomAD3 genomes AF: 0.00000777 AC: 1 AN: 128716 Hom.: 0 Cov.: 18

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

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: 0.0000168

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000230 AC: 3 AN: 130352 AF XY: 0.0000285

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000625

Gnomad OTH exome AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.0000223 AC: 19 AN: 853122 Hom.: 0 Cov.: 12 AF XY: 0.0000297 AC XY: 13 AN XY: 437674

African (AFR) AF: 0.0000419 AC: 1 AN: 23876

American (AMR) AF: 0.00 AC: 0 AN: 34266

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 20766

East Asian (EAS) AF: 0.00 AC: 0 AN: 33872

South Asian (SAS) AF: 0.0000281 AC: 2 AN: 71118

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 44514

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3140

European-Non Finnish (NFE) AF: 0.0000275 AC: 16 AN: 581104

Other (OTH) AF: 0.00 AC: 0 AN: 40466

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.00000777 AC: 1 AN: 128716 Hom.: 0 Cov.: 18 AF XY: 0.00 AC XY: 0 AN XY: 61896

African (AFR) AF: 0.00 AC: 0 AN: 33718

American (AMR) AF: 0.00 AC: 0 AN: 12848

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3032

East Asian (EAS) AF: 0.00 AC: 0 AN: 4530

South Asian (SAS) AF: 0.00 AC: 0 AN: 3662

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 8702

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

European-Non Finnish (NFE) AF: 0.0000168 AC: 1 AN: 59486

Other (OTH) AF: 0.00 AC: 0 AN: 1716

Alfa AF: 0.00 Hom.: 0

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.57
CADD	Benign	8.1
DANN	Benign	0.86
PhyloP100		-2.9

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

Other links and lift over

dbSNP: rs1203694843; hg19: chr6-32009578;