rs1128141

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2BP4_StrongBP7

The NM_018475.5(TMEM165):​c.18A>C​(p.Pro6Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. P6P) has been classified as Benign.

Frequency

Genomes: not found (cov: 33)
Exomes 𝑓: 0.0 ( 0 hom. )
Failed GnomAD Quality Control

Consequence

TMEM165
NM_018475.5 synonymous

Scores

2

Clinical Significance

Not reported in ClinVar

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

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -3 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.95).
BP7
Synonymous conserved (PhyloP=0.111 with no splicing effect.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
TMEM165NM_018475.5 linkc.18A>C p.Pro6Pro synonymous_variant Exon 1 of 6 ENST00000381334.10 NP_060945.2 Q9HC07-1
TMEM165XM_011534394.4 linkc.18A>C p.Pro6Pro synonymous_variant Exon 1 of 6 XP_011532696.1
TMEM165NR_073070.2 linkn.251A>C non_coding_transcript_exon_variant Exon 1 of 7
TMEM165XM_017008412.2 linkc.-428A>C 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
TMEM165ENST00000381334.10 linkc.18A>C p.Pro6Pro synonymous_variant Exon 1 of 6 1 NM_018475.5 ENSP00000370736.5 Q9HC07-1

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD4 exome
Data not reliable, filtered out with message: AC0
AF:
0.00
AC:
0
AN:
1286554
Hom.:
0
Cov.:
55
AF XY:
0.00
AC XY:
0
AN XY:
632800
African (AFR)
AF:
0.00
AC:
0
AN:
26352
American (AMR)
AF:
0.00
AC:
0
AN:
23386
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
22376
East Asian (EAS)
AF:
0.00
AC:
0
AN:
27600
South Asian (SAS)
AF:
0.00
AC:
0
AN:
65046
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
32504
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
4912
European-Non Finnish (NFE)
AF:
0.00
AC:
0
AN:
1031186
Other (OTH)
AF:
0.00
AC:
0
AN:
53192
GnomAD4 genome
Cov.:
33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.95
CADD
Benign
8.1
DANN
Benign
0.22
PhyloP100
0.11
PromoterAI
0.027
Neutral
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.6
Mutation Taster
=299/1
polymorphism

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

Other links and lift over

dbSNP: rs1128141; hg19: chr4-56262374; API