rs255561

Positions:

• chr5-83054991-C-A
• chr5-83054991-C-G
• chr5-83054991-C-T

Variant summary

Our verdict is Benign. Variant got -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

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]

ACMG classification

Verdict is Benign. Variant got -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/exons	MANE	Protein	UniProt
TMEM167A	NM_174909.5	c.*2093G>T		3_prime_UTR_variant	4/4	ENST00000502346.2	NP_777569.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TMEM167A	ENST00000502346.2	c.*2093G>T		3_prime_UTR_variant	4/4	1	NM_174909.5	ENSP00000424707	P1
TMEM167A	ENST00000511450.5	n.2424G>T		non_coding_transcript_exon_variant	5/5	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

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

Gnomad4 AFR AF: 0.593

Gnomad4 AMR AF: 0.348

Gnomad4 ASJ AF: 0.401

Gnomad4 EAS AF: 0.203

Gnomad4 SAS AF: 0.532

Gnomad4 FIN AF: 0.502

Gnomad4 NFE AF: 0.473

Gnomad4 OTH AF: 0.455

Alfa AF: 0.460 Hom.: 33332

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
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0

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

Publications

LitVar

Other links and lift over

dbSNP: rs255561; hg19: chr5-82350810;