19-16501171-C-G

Position:

• chr19-16501171-C-G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_032207.4(C19orf44):​c.379C>G​(p.Leu127Val) 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. 13/19 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: C19orf44 NM_032207.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.916

Genes affected

C19orf44 (HGNC:26141): (chromosome 19 open reading frame 44)

ENSG00000141979 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.17645809).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
C19orf44	NM_032207.4	c.379C>G	p.Leu127Val	missense_variant	2/9	ENST00000221671.8	NP_115583.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
C19orf44	ENST00000221671.8	c.379C>G	p.Leu127Val	missense_variant	2/9	2	NM_032207.4	ENSP00000221671.2
ENSG00000141979	ENST00000409035.1	n.*380-5319G>C		intron_variant		2		ENSP00000386951.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 41

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

Nov 09, 2021

The c.379C>G (p.L127V) alteration is located in exon 2 (coding exon 1) of the C19orf44 gene. This alteration results from a C to G substitution at nucleotide position 379, causing the leucine (L) at amino acid position 127 to be replaced by a valine (V). 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	0.088
BayesDel_addAF	Benign	-0.15	T
BayesDel_noAF	Benign	-0.46
CADD	Benign	17
DANN	Uncertain	0.99
DEOGEN2	Benign	0.077	T;T
Eigen	Benign	-0.096
Eigen_PC	Benign	-0.31
FATHMM_MKL	Benign	0.14	N
LIST_S2	Benign	0.56	T;T
M_CAP	Benign	0.0039	T
MetaRNN	Benign	0.18	T;T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	1.8	L;.
PROVEAN	Benign	-1.0	N;.
REVEL	Benign	0.11
Sift	Benign	0.097	T;.
Sift4G	Benign	0.25	T;T
Polyphen		0.99	D;.
Vest4		0.21
MutPred		0.12		Loss of glycosylation at K129 (P = 0.208);Loss of glycosylation at K129 (P = 0.208);
MVP		0.067
MPC		0.59
ClinPred		0.35	T
GERP RS		2.6
Varity_R		0.11
gMVP		0.080

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: chr19-16611982;