rs6869366

Variant names:

• chr5-83075927-T-G
• rs6869366
• NM_174909.5:c.3+1394A>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_174909.5(TMEM167A):​c.3+1394A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0918 in 152,160 control chromosomes in the GnomAD database, including 868 homozygotes. 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 0.092 (868 hom., cov: 32)
• Consequence: TMEM167A NM_174909.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.69
• Publications: 59 publications found

Genes affected

TMEM167A (HGNC:28330): (transmembrane protein 167A) Involved in constitutive secretory pathway. Located in Golgi apparatus. [provided by Alliance of Genome Resources, Apr 2022]

TMEM167A Gene-Disease associations (from GenCC):

• neonatal diabetes mellitus

  Inheritance: AR Classification: LIMITED Submitted by: Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.77).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.177 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_174909.5. 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
	TMEM167A	NM_174909.5	MANE Select	c.3+1394A>C		intron	N/A	NP_777569.1	Q8TBQ9

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TMEM167A	ENST00000502346.2	TSL:1 MANE Select	c.3+1394A>C		intron	N/A	ENSP00000424707.1	Q8TBQ9
	TMEM167A	ENST00000503892.1	TSL:4	n.146+1791A>C		intron	N/A
	TMEM167A	ENST00000504622.5	TSL:2	n.133+1394A>C		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.0919 AC: 13966 AN: 152042 Hom.: 867 Cov.: 32

Gnomad AFR AF: 0.181

Gnomad AMI AF: 0.0713

Gnomad AMR AF: 0.0593

Gnomad ASJ AF: 0.0268

Gnomad EAS AF: 0.0766

Gnomad SAS AF: 0.171

Gnomad FIN AF: 0.0659

Gnomad MID AF: 0.0886

Gnomad NFE AF: 0.0487

Gnomad OTH AF: 0.0774

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

GnomAD4 genome AF: 0.0918 AC: 13973 AN: 152160 Hom.: 868 Cov.: 32 AF XY: 0.0929 AC XY: 6908 AN XY: 74398

African (AFR) AF: 0.181 AC: 7487 AN: 41466

American (AMR) AF: 0.0592 AC: 905 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.0268 AC: 93 AN: 3470

East Asian (EAS) AF: 0.0768 AC: 398 AN: 5184

South Asian (SAS) AF: 0.171 AC: 827 AN: 4824

European-Finnish (FIN) AF: 0.0659 AC: 699 AN: 10602

Middle Eastern (MID) AF: 0.0816 AC: 24 AN: 294

European-Non Finnish (NFE) AF: 0.0487 AC: 3312 AN: 68004

Other (OTH) AF: 0.0771 AC: 163 AN: 2114

Alfa AF: 0.0738 Hom.: 76

Bravo AF: 0.0913

Asia WGS AF: 0.134 AC: 468 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
CADD	Benign	8.8
DANN	Benign	0.77
PhyloP100		1.7
Mutation Taster		=100/0	polymorphism (auto)

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: rs6869366; hg19: chr5-82371746;