chr19-14600037-G-C

Position:

• chr19-14600037-G-C

Variant summary

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

The NM_001204118.2(CLEC17A):​c.749G>C​(p.Arg250Pro) 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 (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R250C) has been classified 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: -0.827

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=0.056812674).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CLEC17A	NM_001204118.2	c.749G>C	p.Arg250Pro	missense_variant	12/14	ENST00000417570.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CLEC17A	ENST00000417570.6	c.749G>C	p.Arg250Pro	missense_variant	12/14	1	NM_001204118.2	P1
CLEC17A	ENST00000339847.9	c.742+225G>C		intron_variant, NMD_transcript_variant		1
CLEC17A	ENST00000551730.1	c.*128G>C		3_prime_UTR_variant, NMD_transcript_variant	12/14	1
CLEC17A	ENST00000547437.5	c.749G>C	p.Arg250Pro	missense_variant	12/13	2

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

Sep 16, 2021

The c.749G>C (p.R250P) alteration is located in exon 12 (coding exon 12) of the CLEC17A gene. This alteration results from a G to C substitution at nucleotide position 749, causing the arginine (R) at amino acid position 250 to be replaced by a proline (P). 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	0.13
BayesDel_addAF	Benign	-0.27	T
BayesDel_noAF	Benign	-0.62
CADD	Benign	0.61
DANN	Benign	0.37
DEOGEN2	Benign	0.012	.;T
Eigen	Benign	-1.8
Eigen_PC	Benign	-1.8
FATHMM_MKL	Benign	0.0039	N
LIST_S2	Benign	0.27	T;T
M_CAP	Benign	0.0070	T
MetaRNN	Benign	0.057	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-0.69	N;N
MutationTaster	Benign	1.0	N;N;N
PrimateAI	Benign	0.34	T
PROVEAN	Benign	-0.99	N;N
REVEL	Benign	0.13
Sift	Benign	0.14	T;T
Sift4G	Benign	0.27	T;T
Polyphen		0.0	B;B
Vest4		0.14
MutPred		0.58		Loss of stability (P = 0.0949);Loss of stability (P = 0.0949);
MVP		0.13
MPC		0.14
ClinPred		0.078	T
GERP RS		-6.2
Varity_R		0.16
gMVP		0.70

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.15		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: chr19-14710849;