1-19695115-C-T

Variant names:

• chr1-19695115-C-T
• rs74056969
• NM_181719.7:c.1383-564G>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.1383-564G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0812 in 152,254 control chromosomes in the GnomAD database, including 1,593 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 0.081 (1593 hom., cov: 34)
• Consequence: TMCO4 NM_181719.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.561
• Publications: 0 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=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.273 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_181719.7. 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
	TMCO4	NM_181719.7	MANE Select	c.1383-564G>A		intron	N/A	NP_859070.3
	TMCO4	NM_001349112.3		c.1383-564G>A		intron	N/A	NP_001336041.1	Q5TGY1-1
	TMCO4	NM_001349113.3		c.1383-564G>A		intron	N/A	NP_001336042.1	Q5TGY1-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TMCO4	ENST00000294543.11	TSL:1 MANE Select	c.1383-564G>A		intron	N/A	ENSP00000294543.6	Q5TGY1-1
	TMCO4	ENST00000375127.5	TSL:1	c.1383-564G>A		intron	N/A	ENSP00000364269.1	A0A075B6H3
	TMCO4	ENST00000866952.1		c.1383-564G>A		intron	N/A	ENSP00000537011.1

Frequencies

GnomAD3 genomes AF: 0.0810 AC: 12320 AN: 152136 Hom.: 1585 Cov.: 34

Gnomad AFR AF: 0.277

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0341

Gnomad ASJ AF: 0.0187

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00124

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.00194

Gnomad OTH AF: 0.0675

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

GnomAD4 genome AF: 0.0812 AC: 12365 AN: 152254 Hom.: 1593 Cov.: 34 AF XY: 0.0788 AC XY: 5868 AN XY: 74452

African (AFR) AF: 0.277 AC: 11498 AN: 41516

American (AMR) AF: 0.0341 AC: 521 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.0187 AC: 65 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5166

South Asian (SAS) AF: 0.00104 AC: 5 AN: 4830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10630

Middle Eastern (MID) AF: 0.0102 AC: 3 AN: 294

European-Non Finnish (NFE) AF: 0.00194 AC: 132 AN: 68024

Other (OTH) AF: 0.0668 AC: 141 AN: 2110

Alfa AF: 0.0366 Hom.: 244

Bravo AF: 0.0929

Asia WGS AF: 0.0200 AC: 70 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	1.3
DANN	Benign	0.58
PhyloP100		-0.56
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: rs74056969; hg19: chr1-20021608;