rs7518099

Variant names:

• chr1-165767643-C-T
• rs7518099
• NM_019026.6:c.148+549G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_019026.6(TMCO1):​c.148+549G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.893 in 152,268 control chromosomes in the GnomAD database, including 60,767 homozygotes. 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: 𝑓 0.89 (60767 hom., cov: 32)
• Consequence: TMCO1 NM_019026.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.268
• Publications: 35 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, Laboratory for Molecular Medicine, Orphanet, PanelApp Australia, Illumina
• craniofacial dysmorphism, skeletal anomalies, and impaired intellectual development 1

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

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.968 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TMCO1	NM_019026.6	c.148+549G>A		intron_variant	Intron 2 of 6	ENST00000367881.11	NP_061899.3
TMCO1	NM_001256164.1	c.199+549G>A		intron_variant	Intron 2 of 6		NP_001243093.1
TMCO1	NM_001256165.1	c.112+549G>A		intron_variant	Intron 2 of 6		NP_001243094.1
TMCO1	NR_045818.1	n.242+549G>A		intron_variant	Intron 2 of 6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TMCO1	ENST00000367881.11	c.148+549G>A		intron_variant	Intron 2 of 6	1	NM_019026.6	ENSP00000356856.6

Frequencies

GnomAD3 genomes AF: 0.893 AC: 135794 AN: 152150 Hom.: 60713 Cov.: 32

Gnomad AFR AF: 0.921

Gnomad AMI AF: 0.912

Gnomad AMR AF: 0.878

Gnomad ASJ AF: 0.926

Gnomad EAS AF: 0.991

Gnomad SAS AF: 0.938

Gnomad FIN AF: 0.819

Gnomad MID AF: 0.934

Gnomad NFE AF: 0.877

Gnomad OTH AF: 0.895

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.893 AC: 135907 AN: 152268 Hom.: 60767 Cov.: 32 AF XY: 0.892 AC XY: 66417 AN XY: 74438

African (AFR) AF: 0.921 AC: 38242 AN: 41542

American (AMR) AF: 0.878 AC: 13436 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.926 AC: 3214 AN: 3472

East Asian (EAS) AF: 0.991 AC: 5147 AN: 5194

South Asian (SAS) AF: 0.938 AC: 4531 AN: 4830

European-Finnish (FIN) AF: 0.819 AC: 8668 AN: 10590

Middle Eastern (MID) AF: 0.935 AC: 275 AN: 294

European-Non Finnish (NFE) AF: 0.877 AC: 59673 AN: 68028

Other (OTH) AF: 0.896 AC: 1891 AN: 2110

Alfa AF: 0.885 Hom.: 119116

Bravo AF: 0.897

Asia WGS AF: 0.958 AC: 3331 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	2.8
DANN	Benign	0.39
PhyloP100		-0.27
Mutation Taster		=100/0	polymorphism (auto)

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: rs7518099; hg19: chr1-165736880;