Genetic Variant ASDURF:p.Ser29Ser (chr2-189661607-C-T) – ACMG Classification: Benign (-11 pts)

Variant summary

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

The NM_001353493.2(ASDURF):c.87C>T(p.Ser29Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00795 in 399,366 control chromosomes in the GnomAD database, including 25 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0068 ( 6 hom., cov: 32)

Exomes 𝑓: 0.0087 ( 19 hom. )

Consequence

ASDURF
NM_001353493.2 synonymous

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.231

Variant links:

Genes affected

ASDURF (HGNC:53619): (ASNSD1 upstream open reading frame) Predicted to be located in cytoplasm. [provided by Alliance of Genome Resources, Apr 2022]

ASDURF links:

ENSG00000286165 (HGNC:):

ENSG00000286165 links:

ASNSD1 (HGNC:24910): (asparagine synthetase domain containing 1) Predicted to enable asparagine synthase (glutamine-hydrolyzing) activity. Predicted to be involved in asparagine biosynthetic process and glutamine metabolic process. [provided by Alliance of Genome Resources, Apr 2022]

ASNSD1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -11 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.55).

BP6

Variant 2-189661607-C-T is Benign according to our data. Variant chr2-189661607-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 2651759.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=0.231 with no splicing effect.

BS2

High Homozygotes in GnomAd4 at 6 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ASDURF	NM_001353493.2 link	c.87C>T	p.Ser29Ser	synonymous_variant	Exon 1 of 4	ENST00000607829.6	NP_001340422.1
ASNSD1	NM_019048.4 link	c.-226C>T		5_prime_UTR_variant	Exon 1 of 6	ENST00000260952.9	NP_061921.2	Q9NWL6-1
ASDURF	NM_001353494.2 link	c.87C>T	p.Ser29Ser	synonymous_variant	Exon 1 of 4		NP_001340423.1
ASNSD1	NM_001353497.2 link	c.-172C>T		5_prime_UTR_variant	Exon 1 of 5		NP_001340426.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
ASDURF	ENST00000607829.6 link	c.87C>T	p.Ser29Ser	synonymous_variant	Exon 1 of 4	2	NM_001353493.2	ENSP00000475224.1	L0R819-1
ENSG00000286165	ENST00000606910.5 link	c.87C>T	p.Ser29Ser	synonymous_variant	Exon 1 of 5	3		ENSP00000476091.1	U3KQP1
ASNSD1	ENST00000260952 link	c.-226C>T		5_prime_UTR_variant	Exon 1 of 6	1	NM_019048.4	ENSP00000260952.4	Q9NWL6-1

Frequencies

GnomAD3 genomes

AF:

0.00681

AC:

1037

AN:

152198

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00150

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00288

Gnomad ASJ

AF:

0.000576

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.0249

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.00956

Gnomad OTH

AF:

0.00573

GnomAD3 exomes

AF:

0.00850

AC:

AN:

8584

Hom.:

AF XY:

0.00985

AC XY:

AN XY:

4062

show subpopulations

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 SAS exome

AF:

0.00

Gnomad NFE exome

AF:

0.00954

Gnomad OTH exome

AF:

0.00595

GnomAD4 exome

AF:

0.00865

AC:

2137

AN:

247050

Hom.:

Cov.:

AF XY:

0.00848

AC XY:

1062

AN XY:

125296

show subpopulations

Gnomad4 AFR exome

AF:

0.00139

Gnomad4 AMR exome

AF:

0.00323

Gnomad4 ASJ exome

AF:

0.000974

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000329

Gnomad4 FIN exome

AF:

0.0248

Gnomad4 NFE exome

AF:

0.00924

Gnomad4 OTH exome

AF:

0.00622

GnomAD4 genome

AF:

0.00681

AC:

1037

AN:

152316

Hom.:

Cov.:

AF XY:

0.00690

AC XY:

514

AN XY:

74478

show subpopulations

Gnomad4 AFR

AF:

0.00149

Gnomad4 AMR

AF:

0.00288

Gnomad4 ASJ

AF:

0.000576

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.0249

Gnomad4 NFE

AF:

0.00956

Gnomad4 OTH

AF:

0.00567

Alfa

AF:

0.00762

Hom.:

Bravo

AF:

0.00523

Asia WGS

AF:

0.00115

AC:

AN:

3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Dec 01, 2022

CeGaT Center for Human Genetics Tuebingen

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

ASDURF: BP4, BP7, BS2; ASNSD1: BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.55

CADD

Benign

DANN

Benign

0.83

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.040

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