rs6858749

Variant names:

• chr4-55424270-T-A
• rs6858749
• NM_018475.5:c.793-268T>A

Your query was ambiguous. Multiple possible variants found:

• chr4-55424270-T-A
• chr4-55424270-T-C

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_018475.5(TMEM165):​c.793-268T>A variant causes a intron 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.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: TMEM165 NM_018475.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.74
• Publications: 12 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]

TMEM165 Gene-Disease associations (from GenCC):

• TMEM165-congenital disorder of glycosylation

  Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), G2P, Orphanet, Ambry Genetics

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_018475.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TMEM165	NM_018475.5	MANE Select	c.793-268T>A		intron	N/A	NP_060945.2
	TMEM165	NR_073070.2		n.1129-268T>A		intron	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TMEM165	ENST00000381334.10	TSL:1 MANE Select	c.793-268T>A		intron	N/A	ENSP00000370736.5
	TMEM165	ENST00000515591.1	TSL:2	n.1157T>A		non_coding_transcript_exon	Exon 1 of 2
	TMEM165	ENST00000608091.1	TSL:3	c.301-268T>A		intron	N/A	ENSP00000476531.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 284216 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 148406

African (AFR) AF: 0.00 AC: 0 AN: 7918

American (AMR) AF: 0.00 AC: 0 AN: 9340

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 9236

East Asian (EAS) AF: 0.00 AC: 0 AN: 18106

South Asian (SAS) AF: 0.00 AC: 0 AN: 25410

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 17890

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 1360

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 177606

Other (OTH) AF: 0.00 AC: 0 AN: 17350

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.10
DANN	Benign	0.56
PhyloP100		-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: rs6858749; hg19: chr4-56290437;