rs780719919

Variant names:

• chr17-7436896-C-A
• rs780719919
• NM_178518.3:c.917C>A

Your query was ambiguous. Multiple possible variants found:

• chr17-7436896-C-A
• chr17-7436896-C-G
• chr17-7436896-C-T

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_178518.3(TMEM102):​c.917C>A​(p.Thr306Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000686 in 1,457,430 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. T306I) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: TMEM102 NM_178518.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.578
• Publications: 0 publications found

Genes affected

TMEM102 (HGNC:26722): (transmembrane protein 102) Involved in regulation of mitochondrial outer membrane permeabilization involved in apoptotic signaling pathway; response to cytokine; and signal transduction. Acts upstream of or within positive regulation of T cell migration and positive regulation of cell adhesion. Located in cell surface. Part of protein-containing complex. [provided by Alliance of Genome Resources, Apr 2022]

ENSG00000262624 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.3777965).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_178518.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TMEM102	NM_178518.3	MANE Select	c.917C>A	p.Thr306Asn	missense	Exon 3 of 3	NP_848613.1	Q8N9M5
	TMEM102	NM_001320444.1		c.917C>A	p.Thr306Asn	missense	Exon 2 of 2	NP_001307373.1	Q8N9M5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TMEM102	ENST00000323206.2	TSL:1 MANE Select	c.917C>A	p.Thr306Asn	missense	Exon 3 of 3	ENSP00000315387.1	Q8N9M5
	TMEM102	ENST00000396568.1	TSL:2	c.917C>A	p.Thr306Asn	missense	Exon 2 of 2	ENSP00000379815.1	Q8N9M5
	TMEM102	ENST00000860243.1		c.764C>A	p.Thr255Asn	missense	Exon 3 of 3	ENSP00000530302.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.86e-7 AC: 1 AN: 1457430 Hom.: 0 Cov.: 32 AF XY: 0.00000138 AC XY: 1 AN XY: 725252

African (AFR) AF: 0.00 AC: 0 AN: 33476

American (AMR) AF: 0.00 AC: 0 AN: 44690

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26090

East Asian (EAS) AF: 0.00 AC: 0 AN: 39694

South Asian (SAS) AF: 0.0000116 AC: 1 AN: 86208

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 49432

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5762

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1111742

Other (OTH) AF: 0.00 AC: 0 AN: 60336

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.50
BayesDel_addAF	Benign	-0.19	T
BayesDel_noAF	Benign	-0.51
CADD	Uncertain	24
DANN	Uncertain	0.98
DEOGEN2	Benign	0.0066	T
Eigen	Benign	-0.077
Eigen_PC	Benign	-0.23
FATHMM_MKL	Benign	0.26	N
M_CAP	Benign	0.031	D
MetaRNN	Benign	0.38	T
MetaSVM	Benign	-0.95	T
MutationAssessor	Benign	1.6	L
PhyloP100		0.58
PrimateAI	Uncertain	0.74	T
PROVEAN	Benign	-1.1	N
REVEL	Benign	0.071
Sift	Benign	0.067	T
Sift4G	Pathogenic	0.0	D
Polyphen		1.0	D
Vest4		0.48
MutPred		0.27		Loss of glycosylation at T306 (P = 0.0112)
MVP		0.39
ClinPred		0.86	D
GERP RS		4.2
Varity_R		0.16
gMVP		0.65

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs780719919; hg19: chr17-7340215;