4-55424053-A-G

Variant names:

• chr4-55424053-A-G
• rs534654
• NM_018475.5:c.793-485A>G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_018475.5(TMEM165):​c.793-485A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.812 in 154,444 control chromosomes in the GnomAD database, including 51,158 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 0.81 (50414 hom., cov: 32)
  • Exomes 𝑓: 0.80 (744 hom.)
• Consequence: TMEM165 NM_018475.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.896

Genes affected

TMEM165 (HGNC:30760): (transmembrane protein 165) This gene encodes a predicted transmembrane protein with a perinuclear Golgi-like distribution in fibroblasts. Mutations in this gene are associated with the autosomal recessive disorder congenital disorder of glycosylation, type IIk. Knockdown of this gene's expression causes decreased sialylation in HEK cells and suggests this gene plays a role in terminal Golgi glycosylation. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jul 2012]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.99).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.956 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TMEM165	NM_018475.5	c.793-485A>G		intron_variant	Intron 4 of 5	ENST00000381334.10	NP_060945.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TMEM165	ENST00000381334.10	c.793-485A>G		intron_variant	Intron 4 of 5	1	NM_018475.5	ENSP00000370736.5

Frequencies

GnomAD3 genomes AF: 0.813 AC: 123573 AN: 152066 Hom.: 50383 Cov.: 32

Gnomad AFR AF: 0.797

Gnomad AMI AF: 0.640

Gnomad AMR AF: 0.811

Gnomad ASJ AF: 0.805

Gnomad EAS AF: 0.979

Gnomad SAS AF: 0.956

Gnomad FIN AF: 0.840

Gnomad MID AF: 0.854

Gnomad NFE AF: 0.798

Gnomad OTH AF: 0.816

GnomAD4 exome AF: 0.804 AC: 1817 AN: 2260 Hom.: 744 Cov.: 0 AF XY: 0.813 AC XY: 1026 AN XY: 1262

Gnomad4 AFR exome AF: 0.893

Gnomad4 AMR exome AF: 0.873

Gnomad4 ASJ exome AF: 0.769

Gnomad4 EAS exome AF: 0.967

Gnomad4 SAS exome AF: 0.929

Gnomad4 FIN exome AF: 0.871

Gnomad4 NFE exome AF: 0.788

Gnomad4 OTH exome AF: 0.763

GnomAD4 genome AF: 0.813 AC: 123652 AN: 152184 Hom.: 50414 Cov.: 32 AF XY: 0.818 AC XY: 60894 AN XY: 74416

Gnomad4 AFR AF: 0.797

Gnomad4 AMR AF: 0.811

Gnomad4 ASJ AF: 0.805

Gnomad4 EAS AF: 0.979

Gnomad4 SAS AF: 0.956

Gnomad4 FIN AF: 0.840

Gnomad4 NFE AF: 0.798

Gnomad4 OTH AF: 0.819

Alfa AF: 0.804 Hom.: 103941

Bravo AF: 0.806

Asia WGS AF: 0.947 AC: 3296 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	1.1
DANN	Benign	0.49

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: rs534654; hg19: chr4-56290220;