4-55424270-T-C

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_018475.5(TMEM165):c.793-268T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.512 in 435,004 control chromosomes in the GnomAD database, including 60,625 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.46 (17762 hom., cov: 33)
  • Exomes 𝑓: 0.54 (42863 hom.)
• Consequence: TMEM165 NM_018475.5 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.74

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BP6: Variant 4-55424270-T-C is Benign according to our data. Variant chr4-55424270-T-C is described in ClinVar as [Benign]. Clinvar id is 1242762.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.858 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TMEM165	NM_018475.5	c.793-268T>C		intron_variant		ENST00000381334.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TMEM165	ENST00000381334.10	c.793-268T>C		intron_variant		1	NM_018475.5	P1

Frequencies

GnomAD3 genomes AF: 0.462 AC: 70273 AN: 151942 Hom.: 17758 Cov.: 33

Gnomad AFR AF: 0.264

Gnomad AMI AF: 0.368

Gnomad AMR AF: 0.541

Gnomad ASJ AF: 0.567

Gnomad EAS AF: 0.880

Gnomad SAS AF: 0.584

Gnomad FIN AF: 0.483

Gnomad MID AF: 0.585

Gnomad NFE AF: 0.517

Gnomad OTH AF: 0.493

GnomAD4 exome AF: 0.539 AC: 152445 AN: 282944 Hom.: 42863 Cov.: 0 AF XY: 0.541 AC XY: 79994 AN XY: 147750

Gnomad4 AFR exome AF: 0.244

Gnomad4 AMR exome AF: 0.560

Gnomad4 ASJ exome AF: 0.581

Gnomad4 EAS exome AF: 0.842

Gnomad4 SAS exome AF: 0.580

Gnomad4 FIN exome AF: 0.491

Gnomad4 NFE exome AF: 0.516

Gnomad4 OTH exome AF: 0.536

GnomAD4 genome AF: 0.462 AC: 70272 AN: 152060 Hom.: 17762 Cov.: 33 AF XY: 0.467 AC XY: 34727 AN XY: 74328

Gnomad4 AFR AF: 0.263

Gnomad4 AMR AF: 0.541

Gnomad4 ASJ AF: 0.567

Gnomad4 EAS AF: 0.880

Gnomad4 SAS AF: 0.583

Gnomad4 FIN AF: 0.483

Gnomad4 NFE AF: 0.517

Gnomad4 OTH AF: 0.498

Alfa AF: 0.496 Hom.: 4778

Bravo AF: 0.461

Asia WGS AF: 0.665 AC: 2313 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jul 27, 2018

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
Cadd	Benign	0.12
Dann	Benign	0.37

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: rs6858749; hg19: chr4-56290437;