chr8-55762761-T-C

Variant names:

• chr8-55762761-T-C
• NM_001286657.2:c.199A>G

Variant summary

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

The NM_001286657.2(TMEM68):​c.199A>G​(p.Thr67Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: TMEM68 NM_001286657.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.26
• Publications: 0 publications found

Genes affected

TMEM68 (HGNC:26510): (transmembrane protein 68) Predicted to enable acyltransferase activity. Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

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=0.27290362).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001286657.2. 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
	TMEM68	NM_001286657.2	MANE Select	c.199A>G	p.Thr67Ala	missense	Exon 3 of 8	NP_001273586.1	Q96MH6-1
	TMEM68	NM_001363176.1		c.199A>G	p.Thr67Ala	missense	Exon 3 of 8	NP_001350105.1	Q96MH6-1
	TMEM68	NM_152417.3		c.199A>G	p.Thr67Ala	missense	Exon 3 of 6	NP_689630.1	Q96MH6-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TMEM68	ENST00000434581.7	TSL:5 MANE Select	c.199A>G	p.Thr67Ala	missense	Exon 3 of 8	ENSP00000395204.2	Q96MH6-1
	TMEM68	ENST00000521229.5	TSL:1	c.199A>G	p.Thr67Ala	missense	Exon 3 of 3	ENSP00000429210.1	Q96MH6-3
	TMEM68	ENST00000617782.4	TSL:5	c.199A>G	p.Thr67Ala	missense	Exon 2 of 7	ENSP00000478242.1	Q96MH6-1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.67
BayesDel_addAF	Uncertain	0.092	D
BayesDel_noAF	Benign	-0.11
CADD	Benign	21
DANN	Uncertain	1.0
DEOGEN2	Benign	0.056	T
Eigen	Benign	0.17
Eigen_PC	Uncertain	0.26
FATHMM_MKL	Uncertain	0.97	D
LIST_S2	Uncertain	0.88	D
M_CAP	Uncertain	0.088	D
MetaRNN	Benign	0.27	T
MetaSVM	Uncertain	0.35	D
MutationAssessor	Uncertain	2.1	M
PhyloP100		2.3
PrimateAI	Uncertain	0.53	T
PROVEAN	Benign	-1.3	N
REVEL	Uncertain	0.40
Sift	Benign	0.094	T
Sift4G	Benign	0.11	T
Polyphen		0.38	B
Vest4		0.17
MutPred		0.37		Loss of helix (P = 0.0104)
MVP		0.47
MPC		0.42
ClinPred		0.33	T
GERP RS		5.2
PromoterAI		-0.022	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.6
Varity_R		0.079
gMVP		0.76
Mutation Taster		=79/21	polymorphism

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

hg19: chr8-56675320;