rs769539033

Variant names:

• chr4-55396285-G-T
• rs769539033
• NM_018475.5:c.96G>T

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP6_Very_Strong BP7

The NM_018475.5(TMEM165):​c.96G>T​(p.Arg32Arg) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000151 in 1,528,542 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.00083 (1 hom., cov: 33)
  • Exomes 𝑓: 0.000076 (1 hom.)
• Consequence: TMEM165 NM_018475.5 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 0.113
• Publications: 0 publications found

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]

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

ACMG classification

Our verdict: Benign. The variant received -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BP6: Variant 4-55396285-G-T is Benign according to our data. Variant chr4-55396285-G-T is described in ClinVar as [Likely_benign]. Clinvar id is 1612289.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=0.113 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TMEM165	NM_018475.5	c.96G>T	p.Arg32Arg	synonymous_variant	Exon 1 of 6	ENST00000381334.10	NP_060945.2
TMEM165	XM_011534394.4	c.96G>T	p.Arg32Arg	synonymous_variant	Exon 1 of 6		XP_011532696.1
TMEM165	NR_073070.2	n.329G>T		non_coding_transcript_exon_variant	Exon 1 of 7
TMEM165	XM_017008412.2	c.-350G>T		5_prime_UTR_variant	Exon 1 of 8		XP_016863901.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TMEM165	ENST00000381334.10	c.96G>T	p.Arg32Arg	synonymous_variant	Exon 1 of 6	1	NM_018475.5	ENSP00000370736.5

Frequencies

GnomAD3 genomes AF: 0.000829 AC: 126 AN: 152062 Hom.: 1 Cov.: 33

Gnomad AFR AF: 0.00275

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000655

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00318

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000109 AC: 14 AN: 128392 AF XY: 0.000111

Gnomad AFR exome AF: 0.00214

Gnomad AMR exome AF: 0.000213

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.000294

GnomAD4 exome AF: 0.0000763 AC: 105 AN: 1376372 Hom.: 1 Cov.: 34 AF XY: 0.0000558 AC XY: 38 AN XY: 681008

African (AFR) AF: 0.00294 AC: 84 AN: 28562

American (AMR) AF: 0.000142 AC: 5 AN: 35234

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24364

East Asian (EAS) AF: 0.00 AC: 0 AN: 32806

South Asian (SAS) AF: 0.00 AC: 0 AN: 77554

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 39386

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5608

European-Non Finnish (NFE) AF: 9.30e-7 AC: 1 AN: 1075704

Other (OTH) AF: 0.000262 AC: 15 AN: 57154

GnomAD4 genome AF: 0.000828 AC: 126 AN: 152170 Hom.: 1 Cov.: 33 AF XY: 0.000780 AC XY: 58 AN XY: 74404

African (AFR) AF: 0.00274 AC: 114 AN: 41540

American (AMR) AF: 0.000654 AC: 10 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5148

South Asian (SAS) AF: 0.00 AC: 0 AN: 4824

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10608

Middle Eastern (MID) AF: 0.00342 AC: 1 AN: 292

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 67970

Other (OTH) AF: 0.00 AC: 0 AN: 2110

Alfa AF: 0.000641 Hom.: 0

Bravo AF: 0.000865

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

TMEM165-related disorder Benign:1

Aug 08, 2019

PreventionGenetics, part of Exact Sciences

Significance: Likely benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

TMEM165-congenital disorder of glycosylation Benign:1

Jan 21, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not provided Benign:1

Sep 01, 2022

CeGaT Center for Human Genetics Tuebingen

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

TMEM165: BP4, BP7 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	9.9
DANN	Benign	0.57
PhyloP100		0.11
PromoterAI		-0.013	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7

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

Other links and lift over

dbSNP: rs769539033; hg19: chr4-56262452;