1-201152395-T-C

Variant names:

• chr1-201152395-T-C
• rs6694122
• NM_001288565.2:c.67-543A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001288565.2(TMEM9):​c.67-543A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.728 in 152,120 control chromosomes in the GnomAD database, including 40,482 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 0.73 (40482 hom., cov: 32)
• Consequence: TMEM9 NM_001288565.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.12
• Publications: 4 publications found

Genes affected

TMEM9 (HGNC:18823): (transmembrane protein 9) Involved in intracellular pH reduction; positive regulation of canonical Wnt signaling pathway; and proton-transporting V-type ATPase complex assembly. Located in bounding membrane of organelle; intercellular bridge; and mitotic spindle. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.766 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001288565.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TMEM9	NM_001288565.2	MANE Select	c.67-543A>G		intron	N/A	NP_001275494.1
	TMEM9	NM_001288571.2		c.142-543A>G		intron	N/A	NP_001275500.1
	TMEM9	NM_001288570.2		c.76-543A>G		intron	N/A	NP_001275499.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TMEM9	ENST00000367330.6	TSL:1 MANE Select	c.67-543A>G		intron	N/A	ENSP00000356299.1
	TMEM9	ENST00000367333.6	TSL:1	c.67-543A>G		intron	N/A	ENSP00000356302.2
	TMEM9	ENST00000367334.9	TSL:1	c.67-543A>G		intron	N/A	ENSP00000356303.5

Frequencies

GnomAD3 genomes AF: 0.728 AC: 110620 AN: 152002 Hom.: 40459 Cov.: 32

Gnomad AFR AF: 0.652

Gnomad AMI AF: 0.644

Gnomad AMR AF: 0.732

Gnomad ASJ AF: 0.739

Gnomad EAS AF: 0.631

Gnomad SAS AF: 0.740

Gnomad FIN AF: 0.787

Gnomad MID AF: 0.658

Gnomad NFE AF: 0.771

Gnomad OTH AF: 0.724

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

GnomAD4 genome AF: 0.728 AC: 110689 AN: 152120 Hom.: 40482 Cov.: 32 AF XY: 0.727 AC XY: 54065 AN XY: 74360

African (AFR) AF: 0.652 AC: 27043 AN: 41470

American (AMR) AF: 0.732 AC: 11192 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.739 AC: 2565 AN: 3470

East Asian (EAS) AF: 0.632 AC: 3268 AN: 5172

South Asian (SAS) AF: 0.742 AC: 3583 AN: 4832

European-Finnish (FIN) AF: 0.787 AC: 8326 AN: 10586

Middle Eastern (MID) AF: 0.643 AC: 189 AN: 294

European-Non Finnish (NFE) AF: 0.771 AC: 52417 AN: 67976

Other (OTH) AF: 0.719 AC: 1519 AN: 2114

Alfa AF: 0.757 Hom.: 69804

Bravo AF: 0.719

Asia WGS AF: 0.686 AC: 2383 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.15
DANN	Benign	0.66
PhyloP100		-2.1
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs6694122; hg19: chr1-201121523;