rs1128141

Variant names:

• chr4-55396207-A-C
• rs1128141
• NM_018475.5:c.18A>C

Your query was ambiguous. Multiple possible variants found:

• chr4-55396207-A-C
• chr4-55396207-A-G

Variant summary

Our verdict is Likely benign. Variant got -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP7

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.111

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]

ACMG classification

Verdict is Likely_benign. Variant got -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
TMEM165	NM_018475.5	c.18A>C	p.Pro6Pro	synonymous_variant	Exon 1 of 6	ENST00000381334.10	NP_060945.2
TMEM165	XM_011534394.4	c.18A>C	p.Pro6Pro	synonymous_variant	Exon 1 of 6		XP_011532696.1
TMEM165	XM_017008412.2	c.-428A>C		5_prime_UTR_variant	Exon 1 of 8		XP_016863901.1
TMEM165	NR_073070.2	n.251A>C		non_coding_transcript_exon_variant	Exon 1 of 7

Ensembl

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

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

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

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
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.6

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

Other links and lift over

dbSNP: rs1128141; hg19: chr4-56262374;