4-55396207-A-G

Variant names:

Variant summary

Our verdict is Benign. The variant received -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

Publications

15 publications found

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:

SRD5A3-AS1 (HGNC:44138): (SRD5A3 antisense RNA 1)

SRD5A3-AS1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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.

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	NR_073070.2 link	n.251A>G		non_coding_transcript_exon_variant	Exon 1 of 7
TMEM165	XM_017008412.2 link	c.-428A>G		5_prime_UTR_variant	Exon 1 of 8		XP_016863901.1	Q9HC07-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TMEM165	ENST00000381334.10 link	c.18A>G	p.Pro6Pro	synonymous_variant	Exon 1 of 6	1	NM_018475.5	ENSP00000370736.5		Q9HC07-1

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

GnomAD2 exomes

AF:

0.705

AC:

50923

AN:

72280

AF XY:

0.712

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 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

African (AFR)

AF:

0.840

AC:

22115

AN:

26340

American (AMR)

AF:

0.739

AC:

17234

AN:

23320

Ashkenazi Jewish (ASJ)

AF:

0.663

AC:

14798

AN:

22312

East Asian (EAS)

AF:

0.756

AC:

20846

AN:

27580

South Asian (SAS)

AF:

0.803

AC:

51863

AN:

64620

European-Finnish (FIN)

AF:

0.733

AC:

23713

AN:

32372

Middle Eastern (MID)

AF:

0.624

AC:

3056

AN:

4894

European-Non Finnish (NFE)

AF:

0.636

AC:

655166

AN:

1029890

Other (OTH)

AF:

0.677

AC:

35931

AN:

53046

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.476

Heterozygous variant carriers

15100

30200

45300

60400

75500

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.718

AC:

109013

AN:

151808

Hom.:

39713

Cov.:

AF XY:

0.725

AC XY:

53778

AN XY:

74206

show subpopulations

African (AFR)

AF:

0.833

AC:

34564

AN:

41486

American (AMR)

AF:

0.722

AC:

11029

AN:

15272

Ashkenazi Jewish (ASJ)

AF:

0.657

AC:

2278

AN:

3468

East Asian (EAS)

AF:

0.683

AC:

3482

AN:

5100

South Asian (SAS)

AF:

0.815

AC:

3928

AN:

4822

European-Finnish (FIN)

AF:

0.747

AC:

7852

AN:

10508

Middle Eastern (MID)

AF:

0.603

AC:

176

AN:

292

European-Non Finnish (NFE)

AF:

0.645

AC:

43736

AN:

67844

Other (OTH)

AF:

0.685

AC:

1441

AN:

2104

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1574

3148

4722

6296

7870

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

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

Jul 07, 2017

Eurofins Ntd Llc (ga)

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

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. -

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

(source)

DANN

Benign

0.19

PhyloP100

0.11

PromoterAI

0.036

Neutral

(source)

Mutation Taster

=145/155

disease causing

(source)

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

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4-55396207-A-G

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over