4-55396312-C-T

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 2P and 7B. PM2BP4_StrongBP6_ModerateBP7

The NM_018475.5(TMEM165):​c.123C>T​(p.His41His) 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. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: not found (cov: 32)
Exomes 𝑓: 0.0 ( 0 hom. )
Failed GnomAD Quality Control

Consequence

TMEM165
NM_018475.5 synonymous

Scores

2

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.110

Publications

0 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)

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -5 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.83).
BP6
Variant 4-55396312-C-T is Benign according to our data. Variant chr4-55396312-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 2066563.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
Synonymous conserved (PhyloP=0.11 with no splicing effect.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
TMEM165NM_018475.5 linkc.123C>T p.His41His synonymous_variant Exon 1 of 6 ENST00000381334.10 NP_060945.2 Q9HC07-1
TMEM165XM_011534394.4 linkc.123C>T p.His41His synonymous_variant Exon 1 of 6 XP_011532696.1
TMEM165NR_073070.2 linkn.356C>T non_coding_transcript_exon_variant Exon 1 of 7
TMEM165XM_017008412.2 linkc.-323C>T 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.123C>T p.His41His synonymous_variant Exon 1 of 6 1 NM_018475.5 ENSP00000370736.5 Q9HC07-1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
Data not reliable, filtered out with message: AC0
AF:
0.00
AC:
0
AN:
1374500
Hom.:
0
Cov.:
34
AF XY:
0.00
AC XY:
0
AN XY:
679336
African (AFR)
AF:
0.00
AC:
0
AN:
28650
American (AMR)
AF:
0.00
AC:
0
AN:
34792
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
24380
East Asian (EAS)
AF:
0.00
AC:
0
AN:
33190
South Asian (SAS)
AF:
0.00
AC:
0
AN:
77404
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
39938
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
5600
European-Non Finnish (NFE)
AF:
0.00
AC:
0
AN:
1073430
Other (OTH)
AF:
0.00
AC:
0
AN:
57116
GnomAD4 genome
Cov.:
32

ClinVar

Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

TMEM165-congenital disorder of glycosylation Benign:1
Jan 19, 2022
Labcorp Genetics (formerly Invitae), Labcorp
Significance:Likely benign
Review Status:criteria provided, single submitter
Collection Method:clinical testing

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Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.83
CADD
Benign
10
DANN
Benign
0.79
PhyloP100
0.11
PromoterAI
-0.057
Neutral

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

hg19: chr4-56262479; API