Genetic Variant NM_018475.5:c.793-268T>C (chr4-55424270-T-C) – ACMG Classification: Benign (-20 pts)

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

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

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -1.74

Variant links:

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]

TMEM165 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 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_multiple_submitters_no_conflicts, 2 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 rank	MANE	Protein	UniProt
TMEM165	NM_018475.5 link	c.793-268T>C		intron_variant	Intron 4 of 5	ENST00000381334.10	NP_060945.2	Q9HC07-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TMEM165	ENST00000381334.10 link	c.793-268T>C		intron_variant	Intron 4 of 5	1	NM_018475.5	ENSP00000370736.5		Q9HC07-1

Frequencies

GnomAD3 genomes

AF:

0.462

AC:

70273

AN:

151942

Hom.:

17758

Cov.:

show subpopulations

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.:

AF XY:

0.541

AC XY:

79994

AN XY:

147750

show subpopulations

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.:

AF XY:

0.467

AC XY:

34727

AN XY:

74328

show subpopulations

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:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Jul 27, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over