Genetic Variant NM_019886.4:c.798T>C (chrX-46574729-T-C) – ACMG Classification: Benign (-21 pts)

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2

The NM_019886.4(CHST7):c.798T>C(p.Asp266Asp) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00332 in 1,208,383 control chromosomes in the GnomAD database, including 41 homozygotes. There are 1,725 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0057 ( 7 hom., 218 hem., cov: 24)

Exomes 𝑓: 0.0031 ( 34 hom. 1507 hem. )

Consequence

CHST7
NM_019886.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 2.04

Variant links:

Genes affected

CHST7 (HGNC:13817): (carbohydrate sulfotransferase 7) This gene is a member of the Gal/GalNAc/GlcNAc (galactose/N-acetylgalactosamine/N-acetylglucosamine) 6-O-sulfotransferase (GST) family. Members of this family encode enzymes that catalyze the specific addition of sulfate groups to distinct hydroxyl and amino groups of carbohydrates. The encoded protein catalyzes the sulfation of 6-hydroxyl group of GalNAc in chondroitin. [provided by RefSeq, Aug 2013]

CHST7 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.64).

BP6

Variant X-46574729-T-C is Benign according to our data. Variant chrX-46574729-T-C is described in ClinVar as [Benign]. Clinvar id is 773924.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=2.05 with no splicing effect.

BS1

Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.00569 (642/112771) while in subpopulation SAS AF= 0.0343 (95/2769). AF 95% confidence interval is 0.0287. There are 7 homozygotes in gnomad4. There are 218 alleles in male gnomad4 subpopulation. Median coverage is 24. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 7 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CHST7	NM_019886.4 link	c.798T>C	p.Asp266Asp	synonymous_variant	Exon 1 of 2	ENST00000276055.4	NP_063939.2	Q9NS84

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CHST7	ENST00000276055.4 link	c.798T>C	p.Asp266Asp	synonymous_variant	Exon 1 of 2	1	NM_019886.4	ENSP00000276055.3		Q9NS84

Frequencies

GnomAD3 genomes

AF:

0.00566

AC:

638

AN:

112718

Hom.:

Cov.:

AF XY:

0.00622

AC XY:

217

AN XY:

34906

show subpopulations

Gnomad AFR

AF:

0.0133

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00111

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.0167

Gnomad SAS

AF:

0.0349

Gnomad FIN

AF:

0.00518

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000338

Gnomad OTH

AF:

0.00394

GnomAD3 exomes

AF:

0.00688

AC:

1187

AN:

172500

Hom.:

AF XY:

0.00793

AC XY:

471

AN XY:

59396

show subpopulations

Gnomad AFR exome

AF:

0.0138

Gnomad AMR exome

AF:

0.000224

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0156

Gnomad SAS exome

AF:

0.0385

Gnomad FIN exome

AF:

0.00470

Gnomad NFE exome

AF:

0.000422

Gnomad OTH exome

AF:

0.00393

GnomAD4 exome

AF:

0.00308

AC:

3370

AN:

1095612

Hom.:

Cov.:

AF XY:

0.00417

AC XY:

1507

AN XY:

361292

show subpopulations

Gnomad4 AFR exome

AF:

0.0119

Gnomad4 AMR exome

AF:

0.000315

Gnomad4 ASJ exome

AF:

0.0000517

Gnomad4 EAS exome

AF:

0.0112

Gnomad4 SAS exome

AF:

0.0381

Gnomad4 FIN exome

AF:

0.00497

Gnomad4 NFE exome

AF:

0.000214

Gnomad4 OTH exome

AF:

0.00594

GnomAD4 genome

AF:

0.00569

AC:

642

AN:

112771

Hom.:

Cov.:

AF XY:

0.00623

AC XY:

218

AN XY:

34969

show subpopulations

Gnomad4 AFR

AF:

0.0134

Gnomad4 AMR

AF:

0.00111

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.0164

Gnomad4 SAS

AF:

0.0343

Gnomad4 FIN

AF:

0.00518

Gnomad4 NFE

AF:

0.000339

Gnomad4 OTH

AF:

0.00649

Alfa

AF:

0.0636

Hom.:

3710

Bravo

AF:

0.00520

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

May 30, 2018

Labcorp Genetics (formerly Invitae), Labcorp

Significance: 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

-0.64

CADD

Benign

DANN

Benign

0.84

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over