chr17-20579877-C-T

Variant names:

• chr17-20579877-C-T
• rs1483556773
• NM_001190790.2:c.134C>T

Variant summary

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

The NM_001190790.2(CDRT15L2):​c.134C>T​(p.Thr45Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000686 in 1,458,732 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: CDRT15L2 NM_001190790.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.0560
• Publications: 0 publications found

Genes affected

CDRT15L2 (HGNC:34075): (CMT1A duplicated region transcript 15 like 2) Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

LOC105371580 (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=0.12974632).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001190790.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CDRT15L2	NM_001190790.2	MANE Select	c.134C>T	p.Thr45Ile	missense	Exon 1 of 2	NP_001177719.1	A8MXV6

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CDRT15L2	ENST00000399044.1	TSL:2 MANE Select	c.134C>T	p.Thr45Ile	missense	Exon 1 of 2	ENSP00000382000.1	A8MXV6
	CDRT15L2	ENST00000661883.1		c.134C>T	p.Thr45Ile	missense	Exon 1 of 3	ENSP00000499342.1	A0A590UJC2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00000432 AC: 1 AN: 231402 AF XY: 0.00

Gnomad AFR exome AF: 0.0000755

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 6.86e-7 AC: 1 AN: 1458732 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 725440

African (AFR) AF: 0.0000299 AC: 1 AN: 33428

American (AMR) AF: 0.00 AC: 0 AN: 44246

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26068

East Asian (EAS) AF: 0.00 AC: 0 AN: 39636

South Asian (SAS) AF: 0.00 AC: 0 AN: 85648

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53230

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5522

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1110706

Other (OTH) AF: 0.00 AC: 0 AN: 60248

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.22
BayesDel_addAF	Benign	-0.33	T
BayesDel_noAF	Benign	-0.72
CADD	Benign	1.6
DANN	Benign	0.62
DEOGEN2	Benign	0.028	T
Eigen	Benign	-0.85
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.0043	N
LIST_S2	Benign	0.32	T
M_CAP	Benign	0.0021	T
MetaRNN	Benign	0.13	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.1	L
PhyloP100		0.056
PrimateAI	Uncertain	0.58	T
PROVEAN	Benign	-0.91	N
REVEL	Benign	0.023
Sift	Benign	0.16	T
Sift4G	Benign	0.11	T
Vest4		0.19
MutPred		0.32		Loss of phosphorylation at T45 (P = 0.0064)
MVP		0.11
MPC		0.39
ClinPred		0.020	T
GERP RS		-0.12
PromoterAI		0.0086	Neutral
Varity_R		0.028
gMVP		0.021

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: rs1483556773; hg19: chr17-20483190;