1-19707613-A-G

Variant names:

• chr1-19707613-A-G
• rs3885191
• NM_181719.7:c.1265-6728T>C

Variant summary

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

The NM_181719.7(TMCO4):​c.1265-6728T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.831 in 152,200 control chromosomes in the GnomAD database, including 53,117 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 0.83 (53117 hom., cov: 31)
• Consequence: TMCO4 NM_181719.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.09
• 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=-1.02).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.947 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.1265-6728T>C		intron	N/A	NP_859070.3
	TMCO4	NM_001349112.3		c.1265-6728T>C		intron	N/A	NP_001336041.1	Q5TGY1-1
	TMCO4	NM_001349113.3		c.1265-6728T>C		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.1265-6728T>C		intron	N/A	ENSP00000294543.6	Q5TGY1-1
	TMCO4	ENST00000375127.5	TSL:1	c.1265-6728T>C		intron	N/A	ENSP00000364269.1	A0A075B6H3
	TMCO4	ENST00000866952.1		c.1265-6728T>C		intron	N/A	ENSP00000537011.1

Frequencies

GnomAD3 genomes AF: 0.831 AC: 126332 AN: 152082 Hom.: 53050 Cov.: 31

Gnomad AFR AF: 0.955

Gnomad AMI AF: 0.811

Gnomad AMR AF: 0.838

Gnomad ASJ AF: 0.783

Gnomad EAS AF: 0.846

Gnomad SAS AF: 0.806

Gnomad FIN AF: 0.742

Gnomad MID AF: 0.785

Gnomad NFE AF: 0.771

Gnomad OTH AF: 0.812

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

GnomAD4 genome AF: 0.831 AC: 126461 AN: 152200 Hom.: 53117 Cov.: 31 AF XY: 0.829 AC XY: 61656 AN XY: 74412

African (AFR) AF: 0.955 AC: 39665 AN: 41544

American (AMR) AF: 0.838 AC: 12815 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.783 AC: 2719 AN: 3472

East Asian (EAS) AF: 0.846 AC: 4375 AN: 5170

South Asian (SAS) AF: 0.805 AC: 3878 AN: 4818

European-Finnish (FIN) AF: 0.742 AC: 7860 AN: 10598

Middle Eastern (MID) AF: 0.793 AC: 233 AN: 294

European-Non Finnish (NFE) AF: 0.771 AC: 52460 AN: 67998

Other (OTH) AF: 0.813 AC: 1716 AN: 2110

Alfa AF: 0.853 Hom.: 21222

Bravo AF: 0.842

Asia WGS AF: 0.840 AC: 2921 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	1.1
DANN	Benign	0.68
PhyloP100		-1.1
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: rs3885191; hg19: chr1-20034106;