chr5-83054991-C-A

Variant names:

• chr5-83054991-C-A
• rs255561
• NM_174909.5:c.*2093G>T

Variant summary

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

The NM_174909.5(TMEM167A):​c.*2093G>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.486 in 151,716 control chromosomes in the GnomAD database, including 18,579 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 0.49 (18579 hom., cov: 31)
  • Failed GnomAD Quality Control
• Consequence: TMEM167A NM_174909.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.906
• Publications: 17 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=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.587 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TMEM167A	NM_174909.5	c.*2093G>T		3_prime_UTR_variant	Exon 4 of 4	ENST00000502346.2	NP_777569.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TMEM167A	ENST00000502346.2	c.*2093G>T		3_prime_UTR_variant	Exon 4 of 4	1	NM_174909.5	ENSP00000424707.1
TMEM167A	ENST00000511450.5	n.2424G>T		non_coding_transcript_exon_variant	Exon 5 of 5	5

Frequencies

GnomAD3 genomes AF: 0.486 AC: 73726 AN: 151598 Hom.: 18562 Cov.: 31

Gnomad AFR AF: 0.593

Gnomad AMI AF: 0.569

Gnomad AMR AF: 0.349

Gnomad ASJ AF: 0.401

Gnomad EAS AF: 0.203

Gnomad SAS AF: 0.533

Gnomad FIN AF: 0.502

Gnomad MID AF: 0.383

Gnomad NFE AF: 0.473

Gnomad OTH AF: 0.458

GnomAD4 exome Data not reliable, filtered out with message: AC0 AC: 0 AN: 0 Hom.: 0 Cov.: 0 AC XY: 0 AN XY: 0

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AC: 0 AN: 0

Other (OTH) AC: 0 AN: 0

GnomAD4 genome AF: 0.486 AC: 73774 AN: 151716 Hom.: 18579 Cov.: 31 AF XY: 0.484 AC XY: 35896 AN XY: 74154

African (AFR) AF: 0.593 AC: 24542 AN: 41388

American (AMR) AF: 0.348 AC: 5295 AN: 15208

Ashkenazi Jewish (ASJ) AF: 0.401 AC: 1385 AN: 3458

East Asian (EAS) AF: 0.203 AC: 1049 AN: 5164

South Asian (SAS) AF: 0.532 AC: 2561 AN: 4816

European-Finnish (FIN) AF: 0.502 AC: 5293 AN: 10546

Middle Eastern (MID) AF: 0.374 AC: 110 AN: 294

European-Non Finnish (NFE) AF: 0.473 AC: 32065 AN: 67830

Other (OTH) AF: 0.455 AC: 956 AN: 2102

Alfa AF: 0.467 Hom.: 72154

Bravo AF: 0.475

Asia WGS AF: 0.387 AC: 1349 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	3.1
DANN	Benign	0.31
PhyloP100		0.91
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
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: rs255561; hg19: chr5-82350810;