20-32137845-A-G

Position:

• chr20-32137845-A-G

Variant summary

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

The NM_014742.4(TM9SF4):​c.229+1672A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.689 in 152,078 control chromosomes in the GnomAD database, including 37,901 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 0.69 (37901 hom., cov: 31)
• Consequence: TM9SF4 NM_014742.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.219

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=-0.95).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.969 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TM9SF4	NM_014742.4	c.229+1672A>G		intron_variant		ENST00000398022.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TM9SF4	ENST00000398022.7	c.229+1672A>G		intron_variant		1	NM_014742.4	P1

Frequencies

GnomAD3 genomes AF: 0.689 AC: 104728 AN: 151960 Hom.: 37833 Cov.: 31

Gnomad AFR AF: 0.885

Gnomad AMI AF: 0.657

Gnomad AMR AF: 0.693

Gnomad ASJ AF: 0.520

Gnomad EAS AF: 0.992

Gnomad SAS AF: 0.527

Gnomad FIN AF: 0.643

Gnomad MID AF: 0.484

Gnomad NFE AF: 0.576

Gnomad OTH AF: 0.655

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

GnomAD4 genome AF: 0.689 AC: 104855 AN: 152078 Hom.: 37901 Cov.: 31 AF XY: 0.692 AC XY: 51408 AN XY: 74330

Gnomad4 AFR AF: 0.885

Gnomad4 AMR AF: 0.694

Gnomad4 ASJ AF: 0.520

Gnomad4 EAS AF: 0.992

Gnomad4 SAS AF: 0.528

Gnomad4 FIN AF: 0.643

Gnomad4 NFE AF: 0.576

Gnomad4 OTH AF: 0.651

Alfa AF: 0.656 Hom.: 5814

Bravo AF: 0.708

Asia WGS AF: 0.770 AC: 2677 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	1.1
DANN	Benign	0.40

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: rs6142618; hg19: chr20-30725648;