rs2251768

Variant names:

• chr1-165769074-A-C
• rs2251768
• ENST00000580248.5:c.-182-805T>G

Your query was ambiguous. Multiple possible variants found:

• chr1-165769074-A-C
• chr1-165769074-A-G
• chr1-165769074-A-T

Variant summary

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

The ENST00000580248.5(TMCO1):​c.-182-805T>G 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: 31)
• Consequence: TMCO1 ENST00000580248.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.43
• Publications: 13 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-AS1 (HGNC:54046): (TMCO1 antisense RNA 1)

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=-0.93).

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000580248.5. 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
	TMCO1-AS1	NR_125374.1		n.146A>C		non_coding_transcript_exon	Exon 1 of 3
	TMCO1	NM_019026.6	MANE Select	c.-323T>G		upstream_gene	N/A	NP_061899.3	Q9UM00-1
	TMCO1	NM_001256164.1		c.-170T>G		upstream_gene	N/A	NP_001243093.1	B7Z591

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TMCO1	ENST00000580248.5	TSL:2	c.-182-805T>G		intron	N/A	ENSP00000462588.1	J3QQY2
	TMCO1-AS1	ENST00000423121.1	TSL:2	n.146A>C		non_coding_transcript_exon	Exon 1 of 2
	TMCO1	ENST00000367881.11	TSL:1 MANE Select	c.-323T>G		upstream_gene	N/A	ENSP00000356856.6	Q9UM00-1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 7

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.13
DANN	Benign	0.27
PhyloP100		-2.4
PromoterAI		0.049	Neutral

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs2251768; hg19: chr1-165738311;