rs1266438

Variant names:

• chr1-19769683-G-T
• rs1266438
• NM_181719.7:c.382+859C>A

Variant summary

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

The NM_181719.7(TMCO4):​c.382+859C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.584 in 151,664 control chromosomes in the GnomAD database, including 26,781 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 0.58 (26781 hom., cov: 32)
• Consequence: TMCO4 NM_181719.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.11
• Publications: 4 publications found

Genes affected

TMCO4 (HGNC:27393): (transmembrane and coiled-coil domains 4) Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

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 (AFR) allele frequency at 95% confidence interval = 0.734 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TMCO4	NM_181719.7	c.382+859C>A		intron_variant	Intron 6 of 15	ENST00000294543.11	NP_859070.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TMCO4	ENST00000294543.11	c.382+859C>A		intron_variant	Intron 6 of 15	1	NM_181719.7	ENSP00000294543.6

Frequencies

GnomAD3 genomes AF: 0.584 AC: 88523 AN: 151546 Hom.: 26728 Cov.: 32

Gnomad AFR AF: 0.740

Gnomad AMI AF: 0.441

Gnomad AMR AF: 0.490

Gnomad ASJ AF: 0.512

Gnomad EAS AF: 0.688

Gnomad SAS AF: 0.597

Gnomad FIN AF: 0.542

Gnomad MID AF: 0.548

Gnomad NFE AF: 0.515

Gnomad OTH AF: 0.548

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

GnomAD4 genome AF: 0.584 AC: 88632 AN: 151664 Hom.: 26781 Cov.: 32 AF XY: 0.584 AC XY: 43266 AN XY: 74116

African (AFR) AF: 0.741 AC: 30621 AN: 41344

American (AMR) AF: 0.490 AC: 7464 AN: 15242

Ashkenazi Jewish (ASJ) AF: 0.512 AC: 1775 AN: 3466

East Asian (EAS) AF: 0.688 AC: 3560 AN: 5178

South Asian (SAS) AF: 0.598 AC: 2867 AN: 4798

European-Finnish (FIN) AF: 0.542 AC: 5684 AN: 10488

Middle Eastern (MID) AF: 0.558 AC: 163 AN: 292

European-Non Finnish (NFE) AF: 0.515 AC: 34936 AN: 67834

Other (OTH) AF: 0.550 AC: 1160 AN: 2110

Alfa AF: 0.531 Hom.: 67734

Bravo AF: 0.585

Asia WGS AF: 0.633 AC: 2203 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	0.15
DANN	Benign	0.49
PhyloP100		-3.1
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: rs1266438; hg19: chr1-20096176;