7-97858352-C-T

Position:

• chr7-97858352-C-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The NM_001673.5(ASNS):​c.829G>A​(p.Ala277Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00179 in 1,614,120 control chromosomes in the GnomAD database, including 39 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★). Synonymous variant affecting the same amino acid position (i.e. A277A) has been classified as Likely benign.

• Frequency:
  • Genomes: 𝑓 0.0094 (17 hom., cov: 32)
  • Exomes 𝑓: 0.0010 (22 hom.)
• Consequence: ASNS NM_001673.5 missense
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: 0.734

Genes affected

ASNS (HGNC:753): (asparagine synthetase (glutamine-hydrolyzing)) The protein encoded by this gene is involved in the synthesis of asparagine. This gene complements a mutation in the temperature-sensitive hamster mutant ts11, which blocks progression through the G1 phase of the cell cycle at nonpermissive temperature. Alternatively spliced transcript variants have been described for this gene. [provided by RefSeq, May 2010]

CZ1P-ASNS (HGNC:):

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0036463737).
• BP6: Variant 7-97858352-C-T is Benign according to our data. Variant chr7-97858352-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 445740.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00935 (1424/152286) while in subpopulation AFR AF= 0.0329 (1367/41544). AF 95% confidence interval is 0.0315. There are 17 homozygotes in gnomad4. There are 695 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 17 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ASNS	NM_001673.5	c.829G>A	p.Ala277Thr	missense_variant	7/13	ENST00000394308.8
CZ1P-ASNS	NR_147989.1	n.2458G>A		non_coding_transcript_exon_variant	13/19

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ASNS	ENST00000394308.8	c.829G>A	p.Ala277Thr	missense_variant	7/13	1	NM_001673.5	P1

Frequencies

GnomAD3 genomes AF: 0.00936 AC: 1424 AN: 152168 Hom.: 18 Cov.: 32

Gnomad AFR AF: 0.0330

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00255

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.0000882

Gnomad OTH AF: 0.00382

GnomAD3 exomes AF: 0.00252 AC: 634 AN: 251402 Hom.: 10 AF XY: 0.00188 AC XY: 255 AN XY: 135880

Gnomad AFR exome AF: 0.0341

Gnomad AMR exome AF: 0.00136

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000217

Gnomad SAS exome AF: 0.0000327

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000193

Gnomad OTH exome AF: 0.000978

GnomAD4 exome AF: 0.00100 AC: 1467 AN: 1461834 Hom.: 22 Cov.: 30 AF XY: 0.000914 AC XY: 665 AN XY: 727226

Gnomad4 AFR exome AF: 0.0317

Gnomad4 AMR exome AF: 0.00143

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.000453

Gnomad4 SAS exome AF: 0.0000232

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000165

Gnomad4 OTH exome AF: 0.00202

GnomAD4 genome AF: 0.00935 AC: 1424 AN: 152286 Hom.: 17 Cov.: 32 AF XY: 0.00933 AC XY: 695 AN XY: 74464

Gnomad4 AFR AF: 0.0329

Gnomad4 AMR AF: 0.00255

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.000207

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000882

Gnomad4 OTH AF: 0.00378

Alfa AF: 0.00168 Hom.: 6

Bravo AF: 0.0107

TwinsUK AF: 0.00 AC: 0

ALSPAC AF: 0.000519 AC: 2

ESP6500AA AF: 0.0336 AC: 148

ESP6500EA AF: 0.000465 AC: 4

ExAC AF: 0.00322 AC: 391

Asia WGS AF: 0.00202 AC: 8 AN: 3478

EpiCase AF: 0.000382

EpiControl AF: 0.000296

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:4

Benign, criteria provided, single submitter	clinical testing	GeneDx	Aug 31, 2020	- -
Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Feb 01, 2024	- -
Likely benign, criteria provided, single submitter	clinical testing	Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics	Feb 23, 2017	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.076
BayesDel_addAF	Benign	-0.61	T
BayesDel_noAF	Benign	-0.62
CADD	Benign	15
DANN	Benign	0.91
DEOGEN2	Benign	0.41	T;T;.;T;.;.;.
Eigen	Benign	-0.43
Eigen_PC	Benign	-0.29
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Benign	0.62	T;.;.;.;.;T;T
MetaRNN	Benign	0.0036	T;T;T;T;T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.94	L;L;.;L;.;.;.
MutationTaster	Benign	0.82	D;D;N;N;N;N;N
PrimateAI	Benign	0.39	T
PROVEAN	Benign	-0.23	N;N;N;N;N;N;N
REVEL	Benign	0.054
Sift	Benign	0.56	T;T;T;T;T;T;T
Sift4G	Benign	0.58	T;T;T;T;T;T;T
Polyphen		0.24	B;B;.;B;.;.;.
Vest4		0.11
MVP		0.52
MPC		0.40
ClinPred		0.0049	T
GERP RS		2.5
Varity_R		0.029
gMVP		0.38

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

Other links and lift over

dbSNP: rs2070159; hg19: chr7-97487664;