chr4-55396207-A-G

Variant names:

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_018475.5(TMEM165):c.18A>G(p.Pro6Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.664 in 1,436,182 control chromosomes in the GnomAD database, including 319,912 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.72 ( 39713 hom., cov: 33)

Exomes 𝑓: 0.66 ( 280199 hom. )

Consequence

TMEM165
NM_018475.5 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: 0.111

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 -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.94).

BP6

Variant 4-55396207-A-G is Benign according to our data. Variant chr4-55396207-A-G is described in ClinVar as [Benign]. Clinvar id is 193395.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr4-55396207-A-G is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=0.111 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.826 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TMEM165	NM_018475.5 link	c.18A>G	p.Pro6Pro	synonymous_variant	Exon 1 of 6	ENST00000381334.10	NP_060945.2	Q9HC07-1
TMEM165	XM_011534394.4 link	c.18A>G	p.Pro6Pro	synonymous_variant	Exon 1 of 6		XP_011532696.1
TMEM165	XM_017008412.2 link	c.-428A>G		5_prime_UTR_variant	Exon 1 of 8		XP_016863901.1	Q9HC07-2
TMEM165	NR_073070.2 link	n.251A>G		non_coding_transcript_exon_variant	Exon 1 of 7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
TMEM165	ENST00000381334.10 link	c.18A>G	p.Pro6Pro	synonymous_variant	Exon 1 of 6	1	NM_018475.5	ENSP00000370736.5	Q9HC07-1
TMEM165	ENST00000506198.5 link	c.18A>G	p.Pro6Pro	synonymous_variant	Exon 1 of 3	2		ENSP00000425449.1	D6RD79
TMEM165	ENST00000508404.5 link	n.18A>G		non_coding_transcript_exon_variant	Exon 1 of 7	2		ENSP00000422639.1	D6RBL0
TMEM165	ENST00000514070.1 link	n.-44A>G		upstream_gene_variant		2

Frequencies

GnomAD3 genomes

AF:

0.718

AC:

108890

AN:

151698

Hom.:

39644

Cov.:

show subpopulations

Gnomad AFR

AF:

0.833

Gnomad AMI

AF:

0.578

Gnomad AMR

AF:

0.722

Gnomad ASJ

AF:

0.657

Gnomad EAS

AF:

0.683

Gnomad SAS

AF:

0.814

Gnomad FIN

AF:

0.747

Gnomad MID

AF:

0.605

Gnomad NFE

AF:

0.645

Gnomad OTH

AF:

0.682

GnomAD3 exomes

AF:

0.705

AC:

50923

AN:

72280

Hom.:

18256

AF XY:

0.712

AC XY:

29924

AN XY:

42016

show subpopulations

Gnomad AFR exome

AF:

0.828

Gnomad AMR exome

AF:

0.751

Gnomad ASJ exome

AF:

0.660

Gnomad EAS exome

AF:

0.636

Gnomad SAS exome

AF:

0.807

Gnomad FIN exome

AF:

0.734

Gnomad NFE exome

AF:

0.635

Gnomad OTH exome

AF:

0.649

GnomAD4 exome

AF:

0.658

AC:

844722

AN:

1284374

Hom.:

280199

Cov.:

AF XY:

0.662

AC XY:

417873

AN XY:

631672

show subpopulations

Gnomad4 AFR exome

AF:

0.840

Gnomad4 AMR exome

AF:

0.739

Gnomad4 ASJ exome

AF:

0.663

Gnomad4 EAS exome

AF:

0.756

Gnomad4 SAS exome

AF:

0.803

Gnomad4 FIN exome

AF:

0.733

Gnomad4 NFE exome

AF:

0.636

Gnomad4 OTH exome

AF:

0.677

GnomAD4 genome

AF:

0.718

AC:

109013

AN:

151808

Hom.:

39713

Cov.:

AF XY:

0.725

AC XY:

53778

AN XY:

74206

show subpopulations

Gnomad4 AFR

AF:

0.833

Gnomad4 AMR

AF:

0.722

Gnomad4 ASJ

AF:

0.657

Gnomad4 EAS

AF:

0.683

Gnomad4 SAS

AF:

0.815

Gnomad4 FIN

AF:

0.747

Gnomad4 NFE

AF:

0.645

Gnomad4 OTH

AF:

0.685

Alfa

AF:

0.687

Hom.:

5594

Bravo

AF:

0.715

Asia WGS

AF:

0.765

AC:

2611

AN:

3412

ClinVar

Significance: Benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:2

Dec 02, 2015

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

Jul 07, 2017

Eurofins Ntd Llc (ga)

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

TMEM165-congenital disorder of glycosylation

Benign:2

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Sep 10, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Congenital disorder of glycosylation

Benign:1

Jun 14, 2016

Illumina Laboratory Services, Illumina

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not provided

Benign:1

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.94

CADD

Benign

9.3

DANN

Benign

0.19

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