19-46493655-C-A

Variant names:

• chr19-46493655-C-A
• rs530301507
• NM_020709.3:c.1811G>T

Variant summary

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

The NM_020709.3(PNMA8B):​c.1811G>T​(p.Arg604Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000657 in 152,182 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 10/16 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. R604K) has been classified as Likely benign.

• Frequency:
  • Genomes: 𝑓 0.0000066 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: PNMA8B NM_020709.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.227
• Publications: 0 publications found

Genes affected

PNMA8B (HGNC:29206): (PNMA family member 8B)

ENSG00000291145 (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=0.1456672).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_020709.3. 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
	PNMA8B	NM_020709.3	MANE Select	c.1811G>T	p.Arg604Met	missense	Exon 1 of 1	NP_065760.1	Q9ULN7-5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PNMA8B	ENST00000599531.2	TSL:6 MANE Select	c.1811G>T	p.Arg604Met	missense	Exon 1 of 1	ENSP00000473036.1	Q9ULN7-5
	PNMA8B	ENST00000594749.1	TSL:5	n.165+2060G>T		intron	N/A
	ENSG00000291145	ENST00000602017.8	TSL:3	n.425-12215G>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152182 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1382788 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 684924

African (AFR) AF: 0.00 AC: 0 AN: 29224

American (AMR) AF: 0.00 AC: 0 AN: 37340

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24676

East Asian (EAS) AF: 0.00 AC: 0 AN: 34224

South Asian (SAS) AF: 0.00 AC: 0 AN: 78146

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 35140

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4338

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1082102

Other (OTH) AF: 0.00 AC: 0 AN: 57598

GnomAD4 genome AF: 0.00000657 AC: 1 AN: 152182 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 74346

African (AFR) AF: 0.00 AC: 0 AN: 41446

American (AMR) AF: 0.00 AC: 0 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5180

South Asian (SAS) AF: 0.00 AC: 0 AN: 4836

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10626

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 314

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 68016

Other (OTH) AF: 0.00 AC: 0 AN: 2094

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.28
BayesDel_addAF	Benign	-0.29	T
BayesDel_noAF	Benign	-0.65
CADD	Benign	15
DANN	Benign	0.81
FATHMM_MKL	Benign	0.030	N
LIST_S2	Benign	0.22	T
M_CAP	Benign	0.031	D
MetaRNN	Benign	0.15	T
PhyloP100		-0.23
PrimateAI	Uncertain	0.58	T
Sift4G	Pathogenic	0.0	D
Vest4		0.19
MVP		0.15
GERP RS		-2.2
Varity_R		0.058
gMVP		0.14
Mutation Taster		=100/0	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: rs530301507; hg19: chr19-46996912;