chr4-55396235-C-T

Variant names:

• chr4-55396235-C-T
• rs1413878798
• NM_018475.5:c.46C>T

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 2P and 7B. PM2 BP4_Strong BP6_Moderate BP7

The NM_018475.5(TMEM165):​c.46C>T​(p.Leu16Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000527 in 1,327,192 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000053 (0 hom.)
• Consequence: TMEM165 NM_018475.5 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.18
• 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: 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=-0.8).
• BP6: Variant 4-55396235-C-T is Benign according to our data. Variant chr4-55396235-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 3703410.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=1.18 with no splicing effect.

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TMEM165	NM_018475.5	MANE Select	c.46C>T	p.Leu16Leu	synonymous	Exon 1 of 6	NP_060945.2
	TMEM165	NR_073070.2		n.279C>T		non_coding_transcript_exon	Exon 1 of 7

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TMEM165	ENST00000381334.10	TSL:1 MANE Select	c.46C>T	p.Leu16Leu	synonymous	Exon 1 of 6	ENSP00000370736.5	Q9HC07-1
	TMEM165	ENST00000882548.1		c.46C>T	p.Leu16Leu	synonymous	Exon 1 of 7	ENSP00000552607.1
	TMEM165	ENST00000882549.1		c.46C>T	p.Leu16Leu	synonymous	Exon 1 of 7	ENSP00000552608.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD2 exomes AF: 0.00 AC: 0 AN: 90208 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

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: 0.00

GnomAD4 exome AF: 0.00000527 AC: 7 AN: 1327192 Hom.: 0 Cov.: 34 AF XY: 0.00000305 AC XY: 2 AN XY: 655158

African (AFR) AF: 0.00 AC: 0 AN: 27124

American (AMR) AF: 0.00 AC: 0 AN: 27330

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 23450

East Asian (EAS) AF: 0.00 AC: 0 AN: 28688

South Asian (SAS) AF: 0.00 AC: 0 AN: 72396

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 35142

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5438

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1052526

Other (OTH) AF: 0.000127 AC: 7 AN: 55098

GnomAD4 genome Cov.: 33

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	TMEM165-congenital disorder of glycosylation (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	11
DANN	Benign	0.79
PhyloP100		1.2
PromoterAI		0.045	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

Other links and lift over

dbSNP: rs1413878798; hg19: chr4-56262402;