NM_001164407.2:c.342+594T>G

Variant names:

• chr17-1708905-A-C
• rs8076112
• NM_001164407.2:c.342+594T>G

Variant summary

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

The NM_001164407.2(TLCD2):​c.342+594T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.156 in 152,116 control chromosomes in the GnomAD database, including 2,445 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 0.16 (2445 hom., cov: 30)
• Consequence: TLCD2 NM_001164407.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.240
• Publications: 11 publications found

Genes affected

TLCD2 (HGNC:33522): (TLC domain containing 2) Involved in several processes, including membrane assembly; phospholipid homeostasis; and regulation of membrane lipid distribution. Located in plasma 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=-0.79).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.509 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001164407.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TLCD2	NM_001164407.2	MANE Select	c.342+594T>G		intron	N/A	NP_001157879.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TLCD2	ENST00000330676.8	TSL:2 MANE Select	c.342+594T>G		intron	N/A	ENSP00000331965.6

Frequencies

GnomAD3 genomes AF: 0.156 AC: 23700 AN: 151998 Hom.: 2448 Cov.: 30

Gnomad AFR AF: 0.0697

Gnomad AMI AF: 0.216

Gnomad AMR AF: 0.160

Gnomad ASJ AF: 0.174

Gnomad EAS AF: 0.527

Gnomad SAS AF: 0.235

Gnomad FIN AF: 0.176

Gnomad MID AF: 0.184

Gnomad NFE AF: 0.169

Gnomad OTH AF: 0.157

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

GnomAD4 genome AF: 0.156 AC: 23707 AN: 152116 Hom.: 2445 Cov.: 30 AF XY: 0.158 AC XY: 11763 AN XY: 74358

African (AFR) AF: 0.0699 AC: 2905 AN: 41542

American (AMR) AF: 0.160 AC: 2439 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.174 AC: 604 AN: 3470

East Asian (EAS) AF: 0.525 AC: 2702 AN: 5142

South Asian (SAS) AF: 0.235 AC: 1135 AN: 4826

European-Finnish (FIN) AF: 0.176 AC: 1861 AN: 10592

Middle Eastern (MID) AF: 0.184 AC: 54 AN: 294

European-Non Finnish (NFE) AF: 0.169 AC: 11481 AN: 67962

Other (OTH) AF: 0.157 AC: 329 AN: 2102

Alfa AF: 0.162 Hom.: 4650

Bravo AF: 0.152

Asia WGS AF: 0.314 AC: 1092 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	5.4
DANN	Benign	0.85
PhyloP100		0.24
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: rs8076112; hg19: chr17-1612199;