rs1993948

Variant names:

• chr5-83076461-T-A
• rs1993948
• NM_174909.5:c.3+860A>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.3+860A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.484 in 152,108 control chromosomes in the GnomAD database, including 18,396 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 0.48 (18396 hom., cov: 33)
• Consequence: TMEM167A NM_174909.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -4.47
• Publications: 7 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=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.577 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TMEM167A	NM_174909.5	c.3+860A>T		intron_variant	Intron 1 of 3	ENST00000502346.2	NP_777569.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TMEM167A	ENST00000502346.2	c.3+860A>T		intron_variant	Intron 1 of 3	1	NM_174909.5	ENSP00000424707.1

Frequencies

GnomAD3 genomes AF: 0.484 AC: 73529 AN: 151990 Hom.: 18380 Cov.: 33

Gnomad AFR AF: 0.583

Gnomad AMI AF: 0.569

Gnomad AMR AF: 0.350

Gnomad ASJ AF: 0.400

Gnomad EAS AF: 0.203

Gnomad SAS AF: 0.534

Gnomad FIN AF: 0.502

Gnomad MID AF: 0.383

Gnomad NFE AF: 0.473

Gnomad OTH AF: 0.456

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

GnomAD4 genome AF: 0.484 AC: 73575 AN: 152108 Hom.: 18396 Cov.: 33 AF XY: 0.482 AC XY: 35827 AN XY: 74354

African (AFR) AF: 0.583 AC: 24177 AN: 41484

American (AMR) AF: 0.350 AC: 5346 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.400 AC: 1388 AN: 3470

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

South Asian (SAS) AF: 0.533 AC: 2571 AN: 4826

European-Finnish (FIN) AF: 0.502 AC: 5298 AN: 10560

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

European-Non Finnish (NFE) AF: 0.473 AC: 32159 AN: 68000

Other (OTH) AF: 0.454 AC: 958 AN: 2112

Alfa AF: 0.485 Hom.: 2238

Bravo AF: 0.472

Asia WGS AF: 0.386 AC: 1345 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.35
DANN	Benign	0.74
PhyloP100		-4.5
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: rs1993948; hg19: chr5-82372280;