rs6089195

Positions:

• chr20-32143520-G-A
• chr20-32143520-G-T

Variant summary

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

The ENST00000398022.7(TM9SF4):​c.652+415G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0991 in 152,116 control chromosomes in the GnomAD database, including 1,555 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 0.099 (1555 hom., cov: 32)
• Consequence: TM9SF4 ENST00000398022.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.158

Genes affected

TM9SF4 (HGNC:30797): (transmembrane 9 superfamily member 4) Involved in several processes, including positive regulation of protein localization; regulation of intracellular pH; and vacuolar proton-transporting V-type ATPase complex assembly. Located in Golgi apparatus and early endosome. [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=-0.85).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.255 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TM9SF4	NM_014742.4	c.652+415G>A		intron_variant		ENST00000398022.7	NP_055557.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TM9SF4	ENST00000398022.7	c.652+415G>A		intron_variant		1	NM_014742.4	ENSP00000381104	P1
TM9SF4	ENST00000217315.9	c.601+415G>A		intron_variant		2		ENSP00000217315

Frequencies

GnomAD3 genomes AF: 0.0990 AC: 15047 AN: 151998 Hom.: 1550 Cov.: 32

Gnomad AFR AF: 0.259

Gnomad AMI AF: 0.0230

Gnomad AMR AF: 0.107

Gnomad ASJ AF: 0.0130

Gnomad EAS AF: 0.0709

Gnomad SAS AF: 0.0454

Gnomad FIN AF: 0.0388

Gnomad MID AF: 0.0475

Gnomad NFE AF: 0.0219

Gnomad OTH AF: 0.0729

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

GnomAD4 genome AF: 0.0991 AC: 15082 AN: 152116 Hom.: 1555 Cov.: 32 AF XY: 0.0987 AC XY: 7341 AN XY: 74390

Gnomad4 AFR AF: 0.259

Gnomad4 AMR AF: 0.107

Gnomad4 ASJ AF: 0.0130

Gnomad4 EAS AF: 0.0707

Gnomad4 SAS AF: 0.0444

Gnomad4 FIN AF: 0.0388

Gnomad4 NFE AF: 0.0219

Gnomad4 OTH AF: 0.0722

Alfa AF: 0.0746 Hom.: 186

Bravo AF: 0.111

Asia WGS AF: 0.0910 AC: 316 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	6.1
DANN	Benign	0.69

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: rs6089195; hg19: chr20-30731323;