chr19-16501235-A-G

Position:

• chr19-16501235-A-G

Variant summary

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

The NM_032207.4(C19orf44):​c.443A>G​(p.Asp148Gly) 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. 14/19 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: -0.514

Genes affected

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

ENSG00000141979 (HGNC:):

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=0.0657298).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
C19orf44	NM_032207.4	c.443A>G	p.Asp148Gly	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.443A>G	p.Asp148Gly	missense_variant	2/9	2	NM_032207.4	ENSP00000221671.2
ENSG00000141979	ENST00000409035.1	n.*380-5383T>C		intron_variant		2		ENSP00000386951.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 34

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

Jul 20, 2021

The c.443A>G (p.D148G) alteration is located in exon 2 (coding exon 1) of the C19orf44 gene. This alteration results from a A to G substitution at nucleotide position 443, causing the aspartic acid (D) at amino acid position 148 to be replaced by a glycine (G). 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	0.059
BayesDel_addAF	Benign	-0.37	T
BayesDel_noAF	Benign	-0.77
CADD	Benign	1.3
DANN	Benign	0.94
DEOGEN2	Benign	0.062	T;T
Eigen	Benign	-1.4
Eigen_PC	Benign	-1.5
FATHMM_MKL	Benign	0.016	N
LIST_S2	Benign	0.59	T;T
M_CAP	Benign	0.0015	T
MetaRNN	Benign	0.066	T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.28	N;.
PROVEAN	Benign	-2.3	N;.
REVEL	Benign	0.015
Sift	Benign	0.38	T;.
Sift4G	Benign	0.33	T;T
Polyphen		0.0030	B;.
Vest4		0.092
MutPred		0.25		Loss of stability (P = 0.0111);Loss of stability (P = 0.0111);
MVP		0.040
MPC		0.18
ClinPred		0.059	T
GERP RS		-4.0
Varity_R		0.058
gMVP		0.10

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.090		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: chr19-16612046;