chr19-14595281-T-A

Position:

• chr19-14595281-T-A

Variant summary

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

The NM_001204118.2(CLEC17A):​c.411T>A​(p.Asn137Lys) 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. 16/21 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)
• Consequence: CLEC17A NM_001204118.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.310

Genes affected

CLEC17A (HGNC:34520): (C-type lectin domain containing 17A) Enables fucose binding activity; identical protein binding activity; and mannose binding activity. Located in cell surface. [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=0.058797687).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CLEC17A	NM_001204118.2	c.411T>A	p.Asn137Lys	missense_variant	8/14	ENST00000417570.6	NP_001191047.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CLEC17A	ENST00000417570.6	c.411T>A	p.Asn137Lys	missense_variant	8/14	1	NM_001204118.2	ENSP00000393719	P1
CLEC17A	ENST00000339847.9	c.411T>A	p.Asn137Lys	missense_variant, NMD_transcript_variant	8/13	1		ENSP00000341620
CLEC17A	ENST00000551730.1	c.411T>A	p.Asn137Lys	missense_variant, NMD_transcript_variant	8/14	1		ENSP00000447424
CLEC17A	ENST00000547437.5	c.411T>A	p.Asn137Lys	missense_variant	8/13	2		ENSP00000450065

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

May 31, 2023

The c.411T>A (p.N137K) alteration is located in exon 8 (coding exon 8) of the CLEC17A gene. This alteration results from a T to A substitution at nucleotide position 411, causing the asparagine (N) at amino acid position 137 to be replaced by a lysine (K). 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	0.19
BayesDel_addAF	Benign	-0.28	T
BayesDel_noAF	Benign	-0.64
CADD	Benign	1.8
DANN	Benign	0.40
DEOGEN2	Benign	0.0082	.;T
Eigen	Benign	-1.4
Eigen_PC	Benign	-1.5
FATHMM_MKL	Benign	0.023	N
LIST_S2	Benign	0.31	T;T
M_CAP	Benign	0.014	T
MetaRNN	Benign	0.059	T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.0	L;L
MutationTaster	Benign	1.0	N;N;N
PrimateAI	Benign	0.38	T
PROVEAN	Benign	-0.77	N;N
REVEL	Benign	0.032
Sift	Benign	0.28	T;T
Sift4G	Benign	0.17	T;T
Polyphen		0.029	B;B
Vest4		0.087
MutPred		0.22		Gain of ubiquitination at N137 (P = 0.0025);Gain of ubiquitination at N137 (P = 0.0025);
MVP		0.12
MPC		0.12
ClinPred		0.22	T
GERP RS		-1.1
Varity_R		0.061
gMVP		0.047

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: chr19-14706093;