NM_001164407.2:c.226C>A

Variant names:

• chr17-1709837-G-T
• NM_001164407.2:c.226C>A

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001164407.2(TLCD2):​c.226C>A​(p.Arg76Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 31)
• Consequence: TLCD2 NM_001164407.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.307

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

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.06243491).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TLCD2	NM_001164407.2	c.226C>A	p.Arg76Ser	missense_variant	Exon 2 of 4	ENST00000330676.8	NP_001157879.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TLCD2	ENST00000330676.8	c.226C>A	p.Arg76Ser	missense_variant	Exon 2 of 4	2	NM_001164407.2	ENSP00000331965.6

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 34

GnomAD4 genome Cov.: 31

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Dec 09, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.226C>A (p.R76S) alteration is located in exon 2 (coding exon 2) of the TLCD2 gene. This alteration results from a C to A substitution at nucleotide position 226, causing the arginine (R) at amino acid position 76 to be replaced by a serine (S). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.13	T
BayesDel_noAF	Benign	-0.43
CADD	Benign	9.9
DANN	Benign	0.71
DEOGEN2	Benign	0.16	T
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.22	N
M_CAP	Uncertain	0.15	D
MetaRNN	Benign	0.062	T
MetaSVM	Benign	-0.86	T
MutationAssessor	Benign	-0.34	N
PrimateAI	Benign	0.34	T
PROVEAN	Benign	0.58	N
REVEL	Benign	0.20
Sift	Benign	0.56	T
Sift4G	Benign	0.16	T
Vest4		0.10
MutPred		0.58		Loss of sheet (P = 0.1158);
MVP		0.16
ClinPred		0.020	T
GERP RS		1.2
Varity_R		0.070
gMVP		0.26

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr17-1613131;