rs6426940

Variant names:

• chr1-165764246-T-C
• rs6426940
• NM_019026.6:c.148+3946A>G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_019026.6(TMCO1):​c.148+3946A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.528 in 152,130 control chromosomes in the GnomAD database, including 21,777 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 0.53 (21777 hom., cov: 33)
• Consequence: TMCO1 NM_019026.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.264

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.699 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TMCO1	NM_019026.6	c.148+3946A>G		intron_variant	Intron 2 of 6	ENST00000367881.11	NP_061899.3
TMCO1	NM_001256164.1	c.199+3946A>G		intron_variant	Intron 2 of 6		NP_001243093.1
TMCO1	NM_001256165.1	c.112+3946A>G		intron_variant	Intron 2 of 6		NP_001243094.1
TMCO1	NR_045818.1	n.242+3946A>G		intron_variant	Intron 2 of 6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TMCO1	ENST00000367881.11	c.148+3946A>G		intron_variant	Intron 2 of 6	1	NM_019026.6	ENSP00000356856.6

Frequencies

GnomAD3 genomes AF: 0.528 AC: 80276 AN: 152012 Hom.: 21757 Cov.: 33

Gnomad AFR AF: 0.430

Gnomad AMI AF: 0.640

Gnomad AMR AF: 0.542

Gnomad ASJ AF: 0.606

Gnomad EAS AF: 0.370

Gnomad SAS AF: 0.717

Gnomad FIN AF: 0.469

Gnomad MID AF: 0.693

Gnomad NFE AF: 0.586

Gnomad OTH AF: 0.538

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

GnomAD4 genome AF: 0.528 AC: 80337 AN: 152130 Hom.: 21777 Cov.: 33 AF XY: 0.527 AC XY: 39219 AN XY: 74370

Gnomad4 AFR AF: 0.430

Gnomad4 AMR AF: 0.542

Gnomad4 ASJ AF: 0.606

Gnomad4 EAS AF: 0.369

Gnomad4 SAS AF: 0.718

Gnomad4 FIN AF: 0.469

Gnomad4 NFE AF: 0.586

Gnomad4 OTH AF: 0.543

Alfa AF: 0.535 Hom.: 3821

Bravo AF: 0.520

Asia WGS AF: 0.584 AC: 2030 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	5.1
DANN	Benign	0.64

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

Publications

LitVar

Other links and lift over

dbSNP: rs6426940; hg19: chr1-165733483;