chr8-55762840-A-T

Variant names:

• chr8-55762840-A-T
• rs186753985
• NM_001286657.2:c.120T>A

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001286657.2(TMEM68):​c.120T>A​(p.Phe40Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,840 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 nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: TMEM68 NM_001286657.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.08
• 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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.18308145).

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.120T>A	p.Phe40Leu	missense	Exon 3 of 8	NP_001273586.1	Q96MH6-1
	TMEM68	NM_001363176.1		c.120T>A	p.Phe40Leu	missense	Exon 3 of 8	NP_001350105.1	Q96MH6-1
	TMEM68	NM_152417.3		c.120T>A	p.Phe40Leu	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.120T>A	p.Phe40Leu	missense	Exon 3 of 8	ENSP00000395204.2	Q96MH6-1
	TMEM68	ENST00000521229.5	TSL:1	c.120T>A	p.Phe40Leu	missense	Exon 3 of 3	ENSP00000429210.1	Q96MH6-3
	TMEM68	ENST00000617782.4	TSL:5	c.120T>A	p.Phe40Leu	missense	Exon 2 of 7	ENSP00000478242.1	Q96MH6-1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461840 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 727216

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26132

East Asian (EAS) AF: 0.00 AC: 0 AN: 39682

South Asian (SAS) AF: 0.00 AC: 0 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53414

Middle Eastern (MID) AF: 0.000173 AC: 1 AN: 5768

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1111992

Other (OTH) AF: 0.00 AC: 0 AN: 60390

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.69
BayesDel_addAF	Uncertain	0.028	T
BayesDel_noAF	Benign	-0.20
CADD	Benign	21
DANN	Uncertain	1.0
DEOGEN2	Benign	0.046	T
Eigen	Benign	-0.14
Eigen_PC	Benign	-0.030
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.92	D
M_CAP	Benign	0.0082	T
MetaRNN	Benign	0.18	T
MetaSVM	Benign	-0.89	T
MutationAssessor	Benign	1.6	L
PhyloP100		2.1
PrimateAI	Uncertain	0.54	T
PROVEAN	Benign	-1.7	N
REVEL	Uncertain	0.45
Sift	Benign	0.48	T
Sift4G	Benign	0.49	T
Polyphen		0.0020	B
Vest4		0.46
MutPred		0.30		Loss of stability (P = 0.4867)
MVP		0.061
MPC		0.74
ClinPred		0.64	D
GERP RS		4.1
PromoterAI		0.029	Neutral
Varity_R		0.091
gMVP		0.77
Mutation Taster		=73/27	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

dbSNP: rs186753985; hg19: chr8-56675399;