rs11589338

chr1-19715480-T-C

Variant summary

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

The NM_181719.7(TMCO4):c.1265-14595A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0829 in 152,304 control chromosomes in the GnomAD database, including 590 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 0.083 (590 hom., cov: 32)
• Consequence: TMCO4 NM_181719.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.709

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0938 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TMCO4	NM_181719.7	c.1265-14595A>G		intron_variant		ENST00000294543.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TMCO4	ENST00000294543.11	c.1265-14595A>G		intron_variant		1	NM_181719.7	P1
TMCO4	ENST00000375127.5	c.1265-14595A>G		intron_variant		1
TMCO4	ENST00000489814.5	n.284-14595A>G		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.0829 AC: 12615 AN: 152186 Hom.: 590 Cov.: 32

Gnomad AFR AF: 0.0825

Gnomad AMI AF: 0.00219

Gnomad AMR AF: 0.0661

Gnomad ASJ AF: 0.118

Gnomad EAS AF: 0.00135

Gnomad SAS AF: 0.0839

Gnomad FIN AF: 0.0603

Gnomad MID AF: 0.0823

Gnomad NFE AF: 0.0957

Gnomad OTH AF: 0.0898

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

GnomAD4 genome AF: 0.0829 AC: 12620 AN: 152304 Hom.: 590 Cov.: 32 AF XY: 0.0812 AC XY: 6050 AN XY: 74488

Gnomad4 AFR AF: 0.0823

Gnomad4 AMR AF: 0.0659

Gnomad4 ASJ AF: 0.118

Gnomad4 EAS AF: 0.00135

Gnomad4 SAS AF: 0.0847

Gnomad4 FIN AF: 0.0603

Gnomad4 NFE AF: 0.0957

Gnomad4 OTH AF: 0.0888

Alfa AF: 0.0971 Hom.: 936

Bravo AF: 0.0832

Asia WGS AF: 0.0320 AC: 111 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
Cadd	Benign	3.7
Dann	Benign	0.83

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: rs11589338; hg19: chr1-20041973;