10-96567509-T-C

Variant names:

• chr10-96567509-T-C
• rs9633703
• NM_020123.4:c.299-2083A>G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_020123.4(TM9SF3):​c.299-2083A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.588 in 152,054 control chromosomes in the GnomAD database, including 28,006 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.59 (28006 hom., cov: 32)
• Consequence: TM9SF3 NM_020123.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.05

Genes affected

TM9SF3 (HGNC:21529): (transmembrane 9 superfamily member 3) Predicted to be involved in protein localization to membrane. Predicted to be located in exocytic vesicle. Predicted to be active in membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.806 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TM9SF3	NM_020123.4	c.299-2083A>G		intron_variant	Intron 2 of 14	ENST00000371142.9	NP_064508.3
TM9SF3	XM_011539976.3	c.353-2083A>G		intron_variant	Intron 2 of 14		XP_011538278.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TM9SF3	ENST00000371142.9	c.299-2083A>G		intron_variant	Intron 2 of 14	1	NM_020123.4	ENSP00000360184.4
TM9SF3	ENST00000443638.1	c.167-2083A>G		intron_variant	Intron 2 of 6	3		ENSP00000401152.1
TM9SF3	ENST00000464654.1	n.261-2083A>G		intron_variant	Intron 2 of 5	5
TM9SF3	ENST00000649367.1	n.637-2083A>G		intron_variant	Intron 2 of 14

Frequencies

GnomAD3 genomes AF: 0.588 AC: 89354 AN: 151936 Hom.: 27989 Cov.: 32

Gnomad AFR AF: 0.371

Gnomad AMI AF: 0.813

Gnomad AMR AF: 0.580

Gnomad ASJ AF: 0.649

Gnomad EAS AF: 0.826

Gnomad SAS AF: 0.727

Gnomad FIN AF: 0.710

Gnomad MID AF: 0.627

Gnomad NFE AF: 0.668

Gnomad OTH AF: 0.593

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.588 AC: 89396 AN: 152054 Hom.: 28006 Cov.: 32 AF XY: 0.593 AC XY: 44087 AN XY: 74330

Gnomad4 AFR AF: 0.371

Gnomad4 AMR AF: 0.581

Gnomad4 ASJ AF: 0.649

Gnomad4 EAS AF: 0.826

Gnomad4 SAS AF: 0.728

Gnomad4 FIN AF: 0.710

Gnomad4 NFE AF: 0.668

Gnomad4 OTH AF: 0.597

Alfa AF: 0.652 Hom.: 14901

Bravo AF: 0.567

Asia WGS AF: 0.725 AC: 2518 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.24
DANN	Benign	0.63

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: rs9633703; hg19: chr10-98327266;