8-55744325-A-T

Variant names:

• chr8-55744325-A-T
• rs7836689
• NM_001286657.2:c.749-705T>A

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_001286657.2(TMEM68):​c.749-705T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.0035 (0 hom., cov: 0)
  • Failed GnomAD Quality Control
• Consequence: TMEM68 NM_001286657.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.00600
• Publications: 1 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: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.02).

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TMEM68	NM_001286657.2	MANE Select	c.749-705T>A		intron	N/A	NP_001273586.1
	TMEM68	NM_001363176.1		c.749-705T>A		intron	N/A	NP_001350105.1
	TMEM68	NM_152417.3		c.688-4107T>A		intron	N/A	NP_689630.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TMEM68	ENST00000434581.7	TSL:5 MANE Select	c.749-705T>A		intron	N/A	ENSP00000395204.2
	TMEM68	ENST00000617782.4	TSL:5	c.749-705T>A		intron	N/A	ENSP00000478242.1
	TMEM68	ENST00000334667.6	TSL:2	c.688-4107T>A		intron	N/A	ENSP00000335416.2

Frequencies

GnomAD3 genomes AF: 0.00375 AC: 33 AN: 8792 Hom.: 0 Cov.: 0

Gnomad AFR AF: 0.00270

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00325

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00535

Gnomad SAS AF: 0.0170

Gnomad FIN AF: 0.0118

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00252

Gnomad OTH AF: 0.00

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.00353 AC: 31 AN: 8786 Hom.: 0 Cov.: 0 AF XY: 0.00344 AC XY: 14 AN XY: 4070

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00216 AC: 4 AN: 1850

American (AMR) AF: 0.00325 AC: 2 AN: 616

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 254

East Asian (EAS) AF: 0.00535 AC: 2 AN: 374

South Asian (SAS) AF: 0.0150 AC: 7 AN: 466

European-Finnish (FIN) AF: 0.0118 AC: 4 AN: 338

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4

European-Non Finnish (NFE) AF: 0.00252 AC: 12 AN: 4754

Other (OTH) AF: 0.00 AC: 0 AN: 84

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.13
DANN	Benign	0.17
PhyloP100		0.0060

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: rs7836689; hg19: chr8-56656884;