rs143559732

chr16-90031485-G-Achr16-90031485-G-C

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS1

The NM_001481.3(GAS8):c.277G>A(p.Val93Met) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000314 in 1,564,318 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 Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0014 (1 hom., cov: 32)
  • Exomes 𝑓: 0.00019 (1 hom.)
• Consequence: GAS8 NM_001481.3 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 7.94

Genes affected

GAS8 (HGNC:4166): (growth arrest specific 8) This gene includes 11 exons spanning 25 kb and maps to a region of chromosome 16 that is sometimes deleted in breast and prostrate cancer. The second intron contains an apparently intronless gene, C16orf3, that is transcribed in the opposite orientation. This gene is a putative tumor suppressor gene. Several transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Oct 2013]

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.008260578).
• BP6: Variant 16-90031485-G-A is Benign according to our data. Variant chr16-90031485-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 542270.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00143 (218/152362) while in subpopulation AFR AF= 0.00491 (204/41588). AF 95% confidence interval is 0.00435. There are 1 homozygotes in gnomad4. There are 98 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GAS8	NM_001481.3	c.277G>A	p.Val93Met	missense_variant	3/11	ENST00000268699.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GAS8	ENST00000268699.9	c.277G>A	p.Val93Met	missense_variant	3/11	1	NM_001481.3	P4

Frequencies

GnomAD3 genomes AF: 0.00143 AC: 218 AN: 152244 Hom.: 1 Cov.: 32

Gnomad AFR AF: 0.00492

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000589

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000192

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00191

GnomAD3 exomes AF: 0.000356 AC: 60 AN: 168440 Hom.: 0 AF XY: 0.000280 AC XY: 25 AN XY: 89364

Gnomad AFR exome AF: 0.00537

Gnomad AMR exome AF: 0.000157

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000829

Gnomad SAS exome AF: 0.0000419

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.000213

GnomAD4 exome AF: 0.000193 AC: 273 AN: 1411956 Hom.: 1 Cov.: 32 AF XY: 0.000165 AC XY: 115 AN XY: 697706

Gnomad4 AFR exome AF: 0.00694

Gnomad4 AMR exome AF: 0.000136

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000274

Gnomad4 SAS exome AF: 0.0000372

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000276

Gnomad4 OTH exome AF: 0.000614

GnomAD4 genome AF: 0.00143 AC: 218 AN: 152362 Hom.: 1 Cov.: 32 AF XY: 0.00132 AC XY: 98 AN XY: 74506

Gnomad4 AFR AF: 0.00491

Gnomad4 AMR AF: 0.000588

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00

Gnomad4 OTH AF: 0.00189

Alfa AF: 0.000235 Hom.: 0

Bravo AF: 0.00160

ESP6500AA AF: 0.00391 AC: 17

ESP6500EA AF: 0.00 AC: 0

ExAC AF: 0.000344 AC: 40

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Primary ciliary dyskinesia 33 Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Invitae

Jan 12, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.27
BayesDel_addAF	Benign	-0.27	T
BayesDel_noAF	Benign	-0.15
Cadd	Pathogenic	27
Dann	Uncertain	1.0
Eigen	Pathogenic	0.82
Eigen_PC	Pathogenic	0.82
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.97	D;D;D;D;D
M_CAP	Benign	0.024	T
MetaRNN	Benign	0.0083	T;T;T;T;T
MetaSVM	Benign	-0.73	T
MutationTaster	Benign	1.0	D;D
PrimateAI	Uncertain	0.66	T
PROVEAN	Benign	-2.0	N;N;N;N;.
REVEL	Benign	0.14
Sift	Uncertain	0.0080	D;D;D;D;.
Sift4G	Uncertain	0.016	D;D;D;D;D
Polyphen		0.99	.;.;.;D;.
Vest4		0.56
MVP		0.39
MPC		0.038
ClinPred		0.10	T
GERP RS		5.8
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.30
gMVP		0.20

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: rs143559732; hg19: chr16-90097893;