rs7555523

Variant names:

• chr1-165749742-C-A
• rs7555523
• NM_019026.6:c.323+2360G>T

Your query was ambiguous. Multiple possible variants found:

• chr1-165749742-C-A
• chr1-165749742-C-G
• chr1-165749742-C-T

Variant summary

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

The NM_019026.6(TMCO1):​c.323+2360G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.881 in 152,146 control chromosomes in the GnomAD database, including 59,111 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 0.88 (59111 hom., cov: 33)
• Consequence: TMCO1 NM_019026.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.174
• Publications: 45 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=-0.97).
• 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.323+2360G>T		intron_variant	Intron 5 of 6	ENST00000367881.11	NP_061899.3
TMCO1	NM_001256164.1	c.374+2360G>T		intron_variant	Intron 5 of 6		NP_001243093.1
TMCO1	NM_001256165.1	c.287+2360G>T		intron_variant	Intron 5 of 6		NP_001243094.1
TMCO1	NR_045818.1	n.417+2360G>T		intron_variant	Intron 5 of 6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TMCO1	ENST00000367881.11	c.323+2360G>T		intron_variant	Intron 5 of 6	1	NM_019026.6	ENSP00000356856.6

Frequencies

GnomAD3 genomes AF: 0.881 AC: 133913 AN: 152030 Hom.: 59064 Cov.: 33

Gnomad AFR AF: 0.881

Gnomad AMI AF: 0.911

Gnomad AMR AF: 0.872

Gnomad ASJ AF: 0.926

Gnomad EAS AF: 0.991

Gnomad SAS AF: 0.937

Gnomad FIN AF: 0.819

Gnomad MID AF: 0.930

Gnomad NFE AF: 0.877

Gnomad OTH AF: 0.883

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

GnomAD4 genome AF: 0.881 AC: 134018 AN: 152146 Hom.: 59111 Cov.: 33 AF XY: 0.881 AC XY: 65505 AN XY: 74388

African (AFR) AF: 0.881 AC: 36573 AN: 41526

American (AMR) AF: 0.872 AC: 13325 AN: 15274

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

East Asian (EAS) AF: 0.991 AC: 5141 AN: 5188

South Asian (SAS) AF: 0.938 AC: 4525 AN: 4824

European-Finnish (FIN) AF: 0.819 AC: 8616 AN: 10526

Middle Eastern (MID) AF: 0.932 AC: 274 AN: 294

European-Non Finnish (NFE) AF: 0.877 AC: 59651 AN: 68018

Other (OTH) AF: 0.884 AC: 1868 AN: 2112

Alfa AF: 0.881 Hom.: 143775

Bravo AF: 0.883

Asia WGS AF: 0.955 AC: 3312 AN: 3470

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	0.33
DANN	Benign	0.45
PhyloP100		-0.17
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: rs7555523; hg19: chr1-165718979;