rs397967679

Variant names:

• chr1-165728260-CTTTT-C
• rs397967679
• NM_019026.6:c.469-143_469-140delAAAA

Your query was ambiguous. Multiple possible variants found:

• chr1-165728260-CTTTT-C
• chr1-165728260-CTTTT-CT
• chr1-165728260-CTTTT-CTT
• chr1-165728260-CTTTT-CTTT
• chr1-165728260-CTTTT-CTTTTT
• chr1-165728260-CTTTT-CTTTTTT
• chr1-165728260-CTTTT-CTTTTTTT

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_019026.6(TMCO1):​c.469-143_469-140delAAAA variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000156 in 319,986 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.0 (0 hom., cov: 31)
  • Exomes 𝑓: 0.000016 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: TMCO1 NM_019026.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.50
• Publications: 0 publications found

Genes affected

TMCO1 (HGNC:18188): (transmembrane and coiled-coil domains 1) This locus encodes a transmembrane protein. Mutations at this locus have been associated with craniofacial dysmorphism, skeletal anomalies, and cognitive disability. Mutations at this locus have also been associated with open angle glaucoma blindness. Alternatively spliced transcript variants have been described. [provided by RefSeq, Jan 2012]

TMCO1 Gene-Disease associations (from GenCC):

• cerebrofaciothoracic dysplasia

  Inheritance: AR Classification: DEFINITIVE, STRONG, MODERATE, SUPPORTIVE Submitted by: Ambry Genetics, Illumina, Laboratory for Molecular Medicine, Orphanet
• craniofacial dysmorphism, skeletal anomalies, and impaired intellectual development 1

  Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), PanelApp Australia, G2P

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_019026.6. 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
	TMCO1	NM_019026.6	MANE Select	c.469-143_469-140delAAAA		intron	N/A	NP_061899.3	Q9UM00-1
	TMCO1	NM_001256164.1		c.520-143_520-140delAAAA		intron	N/A	NP_001243093.1	B7Z591
	TMCO1	NM_001256165.1		c.433-143_433-140delAAAA		intron	N/A	NP_001243094.1	B7Z591

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TMCO1	ENST00000367881.11	TSL:1 MANE Select	c.469-143_469-140delAAAA		intron	N/A	ENSP00000356856.6	Q9UM00-1
	TMCO1	ENST00000612311.4	TSL:1	c.622-143_622-140delAAAA		intron	N/A	ENSP00000480514.1	Q9UM00-3
	TMCO1	ENST00000868463.1		c.592-143_592-140delAAAA		intron	N/A	ENSP00000538522.1

Frequencies

GnomAD3 genomes AF: 0.00 AC: 0 AN: 144254 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.0000156 AC: 5 AN: 319986 Hom.: 0 AF XY: 0.0000112 AC XY: 2 AN XY: 178322

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 7968

American (AMR) AF: 0.0000493 AC: 1 AN: 20278

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 8874

East Asian (EAS) AF: 0.00 AC: 0 AN: 13208

South Asian (SAS) AF: 0.0000199 AC: 1 AN: 50196

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 16316

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 1158

European-Non Finnish (NFE) AF: 0.0000107 AC: 2 AN: 187208

Other (OTH) AF: 0.0000677 AC: 1 AN: 14780

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 144254 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 69952

African (AFR) AF: 0.00 AC: 0 AN: 39556

American (AMR) AF: 0.00 AC: 0 AN: 14382

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3354

East Asian (EAS) AF: 0.00 AC: 0 AN: 5008

South Asian (SAS) AF: 0.00 AC: 0 AN: 4540

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 8882

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 304

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 65384

Other (OTH) AF: 0.00 AC: 0 AN: 1954

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		2.5

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs397967679; hg19: chr1-165697497;