1-201143853-A-G

Position:

• chr1-201143853-A-G

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The ENST00000367330.6(TMEM9):​c.366T>C​(p.Tyr122=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.756 in 1,613,680 control chromosomes in the GnomAD database, including 462,034 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 (40465 hom., cov: 32)
  • Exomes 𝑓: 0.76 (421569 hom.)
• Consequence: TMEM9 ENST00000367330.6 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.09

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

Verdict is Benign. Variant got -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.68).
• BP7: Synonymous conserved (PhyloP=1.09 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.766 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TMEM9	NM_001288565.2	c.366T>C	p.Tyr122=	synonymous_variant	4/5	ENST00000367330.6	NP_001275494.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TMEM9	ENST00000367330.6	c.366T>C	p.Tyr122=	synonymous_variant	4/5	1	NM_001288565.2	ENSP00000356299	P4

Frequencies

GnomAD3 genomes AF: 0.728 AC: 110605 AN: 151972 Hom.: 40443 Cov.: 32

Gnomad AFR AF: 0.656

Gnomad AMI AF: 0.644

Gnomad AMR AF: 0.721

Gnomad ASJ AF: 0.739

Gnomad EAS AF: 0.635

Gnomad SAS AF: 0.739

Gnomad FIN AF: 0.787

Gnomad MID AF: 0.668

Gnomad NFE AF: 0.771

Gnomad OTH AF: 0.727

GnomAD3 exomes AF: 0.748 AC: 187870 AN: 251162 Hom.: 70518 AF XY: 0.752 AC XY: 102038 AN XY: 135778

Gnomad AFR exome AF: 0.658

Gnomad AMR exome AF: 0.753

Gnomad ASJ exome AF: 0.748

Gnomad EAS exome AF: 0.634

Gnomad SAS exome AF: 0.748

Gnomad FIN exome AF: 0.787

Gnomad NFE exome AF: 0.771

Gnomad OTH exome AF: 0.747

GnomAD4 exome AF: 0.759 AC: 1108674 AN: 1461590 Hom.: 421569 Cov.: 47 AF XY: 0.759 AC XY: 551712 AN XY: 727104

Gnomad4 AFR exome AF: 0.654

Gnomad4 AMR exome AF: 0.747

Gnomad4 ASJ exome AF: 0.747

Gnomad4 EAS exome AF: 0.656

Gnomad4 SAS exome AF: 0.750

Gnomad4 FIN exome AF: 0.795

Gnomad4 NFE exome AF: 0.766

Gnomad4 OTH exome AF: 0.748

GnomAD4 genome AF: 0.728 AC: 110672 AN: 152090 Hom.: 40465 Cov.: 32 AF XY: 0.727 AC XY: 54016 AN XY: 74328

Gnomad4 AFR AF: 0.655

Gnomad4 AMR AF: 0.721

Gnomad4 ASJ AF: 0.739

Gnomad4 EAS AF: 0.636

Gnomad4 SAS AF: 0.740

Gnomad4 FIN AF: 0.787

Gnomad4 NFE AF: 0.771

Gnomad4 OTH AF: 0.722

Alfa AF: 0.759 Hom.: 57662

Bravo AF: 0.719

Asia WGS AF: 0.684 AC: 2379 AN: 3478

EpiCase AF: 0.764

EpiControl AF: 0.758

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.68
CADD	Benign	2.2
DANN	Benign	0.34
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7

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: rs8158; hg19: chr1-201112981; COSMIC: COSV66243678;