19-16500826-C-G

Variant names:

• chr19-16500826-C-G
• rs776435313
• NM_032207.4:c.34C>G

Variant summary

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

The NM_032207.4(C19orf44):​c.34C>G​(p.Arg12Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000692 in 1,444,678 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R12C) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: C19orf44 NM_032207.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.53
• Publications: 0 publications found

Genes affected

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

C19orf44 Gene-Disease associations (from GenCC):

• inherited retinal dystrophy

  Inheritance: AR Classification: LIMITED Submitted by: Ambry Genetics

ENSG00000141979 (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=0.09036127).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_032207.4. 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
	C19orf44	NM_032207.4	MANE Select	c.34C>G	p.Arg12Gly	missense	Exon 2 of 9	NP_115583.1	Q9H6X5-1
	C19orf44	NM_001288834.2		c.34C>G	p.Arg12Gly	missense	Exon 2 of 8	NP_001275763.1	M0R2B3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	C19orf44	ENST00000221671.8	TSL:2 MANE Select	c.34C>G	p.Arg12Gly	missense	Exon 2 of 9	ENSP00000221671.2	Q9H6X5-1
	C19orf44	ENST00000594035.5	TSL:1	c.34C>G	p.Arg12Gly	missense	Exon 2 of 8	ENSP00000472436.1	M0R2B3
	C19orf44	ENST00000593380.1	TSL:1	n.34C>G		non_coding_transcript_exon	Exon 2 of 9	ENSP00000472255.1	Q9H6X5-2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.92e-7 AC: 1 AN: 1444678 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 718058

African (AFR) AF: 0.00 AC: 0 AN: 32292

American (AMR) AF: 0.00 AC: 0 AN: 40100

Ashkenazi Jewish (ASJ) AF: 0.0000396 AC: 1 AN: 25236

East Asian (EAS) AF: 0.00 AC: 0 AN: 39566

South Asian (SAS) AF: 0.00 AC: 0 AN: 83250

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53208

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5672

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1105766

Other (OTH) AF: 0.00 AC: 0 AN: 59588

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.078
BayesDel_addAF	Benign	-0.31	T
BayesDel_noAF	Benign	-0.69
CADD	Benign	0.023
DANN	Benign	0.72
DEOGEN2	Benign	0.061	T
Eigen	Benign	-1.4
Eigen_PC	Benign	-1.5
FATHMM_MKL	Benign	0.025	N
LIST_S2	Benign	0.48	T
M_CAP	Benign	0.0059	T
MetaRNN	Benign	0.090	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.2	L
PhyloP100		-2.5
PROVEAN	Benign	-1.4	N
REVEL	Benign	0.16
Sift	Benign	0.47	T
Sift4G	Benign	0.21	T
Polyphen		0.044	B
Vest4		0.18
MutPred		0.34		Loss of MoRF binding (P = 0.0145)
MVP		0.048
MPC		0.20
ClinPred		0.11	T
GERP RS		-8.9
Varity_R		0.060
gMVP		0.081
Mutation Taster		=98/2	polymorphism

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

Other links and lift over

dbSNP: rs776435313; hg19: chr19-16611637;