13-102741045-T-G

Variant names:

• chr13-102741045-T-G
• rs796052147
• NM_001146197.3:c.9652A>C

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The ENST00000322527.4(CCDC168):​c.9652A>C​(p.Met3218Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000429 in 1,398,164 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 9/11 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. M3218V) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000043 (0 hom.)
• Consequence: CCDC168 ENST00000322527.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.483
• Publications: 1 publications found

Genes affected

LRTM3 (HGNC:26851): (coiled-coil domain containing 168)

ENSG00000286312 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.081333876).

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000322527.4. 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
	LRTM3	NM_001146197.3	MANE Select	c.9652A>C	p.Met3218Leu	missense	Exon 4 of 4	NP_001139669.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CCDC168	ENST00000322527.4	TSL:3 MANE Select	c.9652A>C	p.Met3218Leu	missense	Exon 4 of 4	ENSP00000320232.3
	ENSG00000286312	ENST00000771848.1		n.194+9133T>G		intron	N/A

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000429 AC: 6 AN: 1398164 Hom.: 0 Cov.: 39 AF XY: 0.00000145 AC XY: 1 AN XY: 689644

African (AFR) AF: 0.00 AC: 0 AN: 31530

American (AMR) AF: 0.00 AC: 0 AN: 35688

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25108

East Asian (EAS) AF: 0.00 AC: 0 AN: 35714

South Asian (SAS) AF: 0.00 AC: 0 AN: 79192

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 49000

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5684

European-Non Finnish (NFE) AF: 0.00000556 AC: 6 AN: 1078312

Other (OTH) AF: 0.00 AC: 0 AN: 57936

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.14
BayesDel_addAF	Benign	-0.18	T
BayesDel_noAF	Benign	-0.49
CADD	Benign	0.13
DANN	Benign	0.67
FATHMM_MKL	Benign	0.0066	N
MetaRNN	Benign	0.081	T
PhyloP100		-0.48
PrimateAI	Benign	0.26	T
Vest4		0.26
MVP		0.076
GERP RS		-1.9
gMVP		0.039

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: rs796052147; hg19: chr13-103393395;