NM_181719.7:c.1501-5363C>T

Variant names:

• chr1-19688807-G-A
• rs16822732
• NM_181719.7:c.1501-5363C>T

Variant summary

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

The NM_181719.7(TMCO4):​c.1501-5363C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.121 in 152,212 control chromosomes in the GnomAD database, including 1,347 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 0.12 (1347 hom., cov: 32)
• Consequence: TMCO4 NM_181719.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.33
• 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=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.244 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TMCO4	NM_181719.7	c.1501-5363C>T		intron_variant	Intron 15 of 15	ENST00000294543.11	NP_859070.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TMCO4	ENST00000294543.11	c.1501-5363C>T		intron_variant	Intron 15 of 15	1	NM_181719.7	ENSP00000294543.6
TMCO4	ENST00000375127.5	c.1501-5363C>T		intron_variant	Intron 14 of 15	1		ENSP00000364269.1
TMCO4	ENST00000489814.5	n.520-5363C>T		intron_variant	Intron 4 of 4	2

Frequencies

GnomAD3 genomes AF: 0.122 AC: 18491 AN: 152094 Hom.: 1349 Cov.: 32

Gnomad AFR AF: 0.0603

Gnomad AMI AF: 0.274

Gnomad AMR AF: 0.112

Gnomad ASJ AF: 0.170

Gnomad EAS AF: 0.256

Gnomad SAS AF: 0.167

Gnomad FIN AF: 0.116

Gnomad MID AF: 0.199

Gnomad NFE AF: 0.144

Gnomad OTH AF: 0.118

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

GnomAD4 genome AF: 0.121 AC: 18485 AN: 152212 Hom.: 1347 Cov.: 32 AF XY: 0.123 AC XY: 9156 AN XY: 74400

African (AFR) AF: 0.0602 AC: 2501 AN: 41536

American (AMR) AF: 0.112 AC: 1706 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.170 AC: 591 AN: 3470

East Asian (EAS) AF: 0.256 AC: 1325 AN: 5182

South Asian (SAS) AF: 0.167 AC: 806 AN: 4820

European-Finnish (FIN) AF: 0.116 AC: 1226 AN: 10600

Middle Eastern (MID) AF: 0.194 AC: 57 AN: 294

European-Non Finnish (NFE) AF: 0.144 AC: 9777 AN: 67992

Other (OTH) AF: 0.117 AC: 247 AN: 2110

Alfa AF: 0.143 Hom.: 302

Bravo AF: 0.117

Asia WGS AF: 0.189 AC: 656 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	0.24
DANN	Benign	0.53
PhyloP100		-2.3
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: rs16822732; hg19: chr1-20015300;