7-130170412-G-A

Position:

• chr7-130170412-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The ENST00000397622.7(TMEM209):​c.1619C>T​(p.Ser540Leu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: TMEM209 ENST00000397622.7 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 9.60

Genes affected

TMEM209 (HGNC:21898): (transmembrane protein 209) Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

TMEM209 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TMEM209	NM_032842.4	c.1619C>T	p.Ser540Leu	missense_variant	14/15	ENST00000397622.7	NP_116231.2
TMEM209	NM_001363478.2	c.1616C>T	p.Ser539Leu	missense_variant	14/15		NP_001350407.1
TMEM209	NM_001301163.2	c.1493C>T	p.Ser498Leu	missense_variant	13/14		NP_001288092.1
TMEM209	NR_156699.2	n.1679C>T		non_coding_transcript_exon_variant	14/15

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TMEM209	ENST00000397622.7	c.1619C>T	p.Ser540Leu	missense_variant	14/15	1	NM_032842.4	ENSP00000380747.2
TMEM209	ENST00000473456.5	c.1493C>T	p.Ser498Leu	missense_variant	13/14	1		ENSP00000417258.1
TMEM209	ENST00000462753.5	c.1616C>T	p.Ser539Leu	missense_variant	14/15	5		ENSP00000419697.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1460016 Hom.: 0 Cov.: 29 AF XY: 0.00 AC XY: 0 AN XY: 726278

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Apr 13, 2023

The c.1619C>T (p.S540L) alteration is located in exon 14 (coding exon 14) of the TMEM209 gene. This alteration results from a C to T substitution at nucleotide position 1619, causing the serine (S) at amino acid position 540 to be replaced by a leucine (L). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.34
BayesDel_addAF	Uncertain	0.12	D
BayesDel_noAF	Uncertain	-0.070
CADD	Pathogenic	32
DANN	Uncertain	1.0
DEOGEN2	Benign	0.082	T;.;.
Eigen	Pathogenic	0.78
Eigen_PC	Pathogenic	0.81
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.96	D;D;D
M_CAP	Benign	0.034	D
MetaRNN	Uncertain	0.74	D;D;D
MetaSVM	Benign	-0.94	T
MutationAssessor	Uncertain	2.2	M;.;.
MutationTaster	Benign	1.0	D;D;D;D
PrimateAI	Pathogenic	0.80	T
PROVEAN	Uncertain	-2.8	D;D;D
REVEL	Uncertain	0.30
Sift	Benign	0.051	T;T;T
Sift4G	Benign	0.18	T;T;T
Polyphen		0.95	P;.;D
Vest4		0.89
MutPred		0.59		Loss of methylation at K536 (P = 0.0475);.;.;
MVP		0.57
MPC		0.14
ClinPred		0.92	D
GERP RS		5.7
Varity_R		0.35
gMVP		0.67

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr7-129810252;