rs772416639

Variant names:

• chr8-55762839-C-A
• rs772416639
• NM_001286657.2:c.121G>T

Your query was ambiguous. Multiple possible variants found:

• chr8-55762839-C-A
• chr8-55762839-C-T

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.121G>T​(p.Ala41Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000041 in 1,461,828 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A41T) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000041 (0 hom.)
• Consequence: TMEM68 NM_001286657.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.0300
• 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=0.1347866).

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.121G>T	p.Ala41Ser	missense	Exon 3 of 8	NP_001273586.1	Q96MH6-1
	TMEM68	NM_001363176.1		c.121G>T	p.Ala41Ser	missense	Exon 3 of 8	NP_001350105.1	Q96MH6-1
	TMEM68	NM_152417.3		c.121G>T	p.Ala41Ser	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.121G>T	p.Ala41Ser	missense	Exon 3 of 8	ENSP00000395204.2	Q96MH6-1
	TMEM68	ENST00000521229.5	TSL:1	c.121G>T	p.Ala41Ser	missense	Exon 3 of 3	ENSP00000429210.1	Q96MH6-3
	TMEM68	ENST00000617782.4	TSL:5	c.121G>T	p.Ala41Ser	missense	Exon 2 of 7	ENSP00000478242.1	Q96MH6-1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD2 exomes AF: 0.00000796 AC: 2 AN: 251204 AF XY: 0.00000736

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000109

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000410 AC: 6 AN: 1461828 Hom.: 0 Cov.: 31 AF XY: 0.00000275 AC XY: 2 AN XY: 727212

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: 26130

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

South Asian (SAS) AF: 0.00 AC: 0 AN: 86256

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

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.00000540 AC: 6 AN: 1111986

Other (OTH) AF: 0.00 AC: 0 AN: 60388

GnomAD4 genome Cov.: 33

ExAC AF: 0.00000824 AC: 1

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	Benign	0.12
BayesDel_addAF	Benign	-0.10	T
BayesDel_noAF	Benign	-0.16
CADD	Benign	18
DANN	Benign	0.93
DEOGEN2	Benign	0.018	T
Eigen	Benign	-0.079
Eigen_PC	Benign	0.062
FATHMM_MKL	Uncertain	0.88	D
LIST_S2	Uncertain	0.90	D
M_CAP	Benign	0.049	D
MetaRNN	Benign	0.13	T
MetaSVM	Uncertain	-0.10	T
MutationAssessor	Benign	0.64	N
PhyloP100		0.030
PrimateAI	Benign	0.29	T
PROVEAN	Benign	-0.33	N
REVEL	Uncertain	0.32
Sift	Benign	0.75	T
Sift4G	Benign	0.58	T
Polyphen		0.0	B
Vest4		0.28
MutPred		0.43		Loss of catalytic residue at A41 (P = 0.0255)
MVP		0.55
MPC		0.48
ClinPred		0.22	T
GERP RS		4.3
PromoterAI		0.031	Neutral
Varity_R		0.067
gMVP		0.67
Mutation Taster		=91/9	polymorphism

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: rs772416639; hg19: chr8-56675398;