19-10093363-C-T

Variant names:

• chr19-10093363-C-T
• rs1055750184
• NM_031917.3:c.1208G>A

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BS2

The NM_031917.3(ANGPTL6):​c.1208G>A​(p.Arg403Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000409 in 1,613,380 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.0000066 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000044 (0 hom.)
• Consequence: ANGPTL6 NM_031917.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.99
• Publications: 0 publications found

Genes affected

ANGPTL6 (HGNC:23140): (angiopoietin like 6) Predicted to enable signaling receptor binding activity. Predicted to be involved in angiogenesis and cell differentiation. Located in extracellular exosome. Part of collagen-containing extracellular matrix. [provided by Alliance of Genome Resources, Apr 2022]

SHFL (HGNC:25649): (shiftless antiviral inhibitor of ribosomal frameshifting) This gene is an interferon stimulated gene (ISG) that inhibits viral replication. The encoded protein binds nucleic acids and inhibits programmed -1 ribosomal frameshifting required for translation by many RNA viruses. Viruses inhibited by the protein include Zika virus, dengue virus and the coronaviruses, SARS-CoV and SARS-CoV2. [provided by RefSeq, Aug 2021]

ACMG classification

Our verdict: Likely_benign. The variant received -4 ACMG points.

• BS2: High AC in GnomAdExome4 at 65 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_031917.3. 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
	ANGPTL6	NM_031917.3	MANE Select	c.1208G>A	p.Arg403Gln	missense	Exon 5 of 6	NP_114123.2
	ANGPTL6	NM_001321411.2		c.1208G>A	p.Arg403Gln	missense	Exon 5 of 6	NP_001308340.1	Q8NI99
	ANGPTL6	NM_001387347.1		c.1208G>A	p.Arg403Gln	missense	Exon 6 of 7	NP_001374276.1	Q8NI99

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ANGPTL6	ENST00000253109.5	TSL:1 MANE Select	c.1208G>A	p.Arg403Gln	missense	Exon 5 of 6	ENSP00000253109.3	Q8NI99
	ANGPTL6	ENST00000592641.5	TSL:1	c.1208G>A	p.Arg403Gln	missense	Exon 5 of 6	ENSP00000467930.1	Q8NI99
	ANGPTL6	ENST00000890998.1		c.1208G>A	p.Arg403Gln	missense	Exon 6 of 7	ENSP00000561057.1

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152134 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

GnomAD2 exomes AF: 0.00000797 AC: 2 AN: 251016 AF XY: 0.0000147

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000176

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000445 AC: 65 AN: 1461246 Hom.: 0 Cov.: 31 AF XY: 0.0000495 AC XY: 36 AN XY: 726796

African (AFR) AF: 0.0000896 AC: 3 AN: 33464

American (AMR) AF: 0.0000447 AC: 2 AN: 44716

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26110

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39676

South Asian (SAS) AF: 0.0000116 AC: 1 AN: 86240

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53410

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5762

European-Non Finnish (NFE) AF: 0.0000486 AC: 54 AN: 1111510

Other (OTH) AF: 0.0000663 AC: 4 AN: 60358

GnomAD4 genome AF: 0.00000657 AC: 1 AN: 152134 Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1 AN XY: 74316

African (AFR) AF: 0.00 AC: 0 AN: 41424

American (AMR) AF: 0.00 AC: 0 AN: 15270

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 5178

South Asian (SAS) AF: 0.00 AC: 0 AN: 4828

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10624

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 68020

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

Alfa AF: 0.000132 Hom.: 0

Bravo AF: 0.0000189

EpiCase AF: 0.0000545

EpiControl AF: 0.00

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.10
BayesDel_addAF	Benign	-0.049	T
BayesDel_noAF	Benign	-0.29
CADD	Pathogenic	26
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.030	T
Eigen	Uncertain	0.27
Eigen_PC	Uncertain	0.33
FATHMM_MKL	Benign	0.16	N
LIST_S2	Uncertain	0.93	D
M_CAP	Benign	0.074	D
MetaRNN	Uncertain	0.46	T
MetaSVM	Uncertain	-0.25	T
MutationAssessor	Benign	-0.14	N
PhyloP100		3.0
PrimateAI	Benign	0.38	T
PROVEAN	Benign	-0.96	N
REVEL	Uncertain	0.33
Sift	Benign	0.10	T
Sift4G	Benign	0.23	T
Polyphen		0.98	D
Vest4		0.38
MVP		0.86
ClinPred		0.76	D
GERP RS		4.5
Varity_R		0.46
gMVP		0.39
Mutation Taster		=78/22	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: rs1055750184; hg19: chr19-10204039;