rs148508323

Variant names:

• chr22-26434300-T-A
• rs148508323
• NM_020437.5:c.685T>A

Your query was ambiguous. Multiple possible variants found:

• chr22-26434300-T-A
• chr22-26434300-T-G

Variant summary

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

The NM_020437.5(ASPHD2):​c.685T>A​(p.Phe229Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,848 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: ASPHD2 NM_020437.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.05

Genes affected

ASPHD2 (HGNC:30437): (aspartate beta-hydroxylase domain containing 2) Predicted to enable dioxygenase activity and metal ion binding activity. Predicted to be involved in peptidyl-amino acid modification. Located in membrane. [provided by Alliance of Genome Resources, Apr 2022]

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=0.061751366).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ASPHD2	NM_020437.5	c.685T>A	p.Phe229Ile	missense_variant	Exon 2 of 4	ENST00000215906.6	NP_065170.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ASPHD2	ENST00000215906.6	c.685T>A	p.Phe229Ile	missense_variant	Exon 2 of 4	1	NM_020437.5	ENSP00000215906.5

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD3 exomes AF: 0.00000398 AC: 1 AN: 251412 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 135884

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 SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000879

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461848 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 727234

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 8.99e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.20
BayesDel_addAF	Benign	-0.20	T
BayesDel_noAF	Benign	-0.52
CADD	Benign	17
DANN	Benign	0.93
DEOGEN2	Benign	0.022	T
Eigen	Benign	-0.53
Eigen_PC	Benign	-0.40
FATHMM_MKL	Uncertain	0.84	D
LIST_S2	Benign	0.68	T
M_CAP	Benign	0.0036	T
MetaRNN	Benign	0.062	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.29	N
PrimateAI	Uncertain	0.49	T
PROVEAN	Benign	-1.1	N
REVEL	Benign	0.080
Sift	Benign	0.38	T
Sift4G	Benign	0.35	T
Polyphen		0.0	B
Vest4		0.21
MutPred		0.40		Loss of sheet (P = 0.0181);
MVP		0.082
MPC		0.78
ClinPred		0.11	T
GERP RS		0.28
Varity_R		0.12
gMVP		0.65

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

LitVar

Other links and lift over

dbSNP: rs148508323; hg19: chr22-26830266;