16-29901583-C-G

Variant names:

• chr16-29901583-C-G
• NM_181718.4:c.612C>G
• ASPHD1 p.Asp204Glu

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_181718.4(ASPHD1):​c.612C>G​(p.Asp204Glu) 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. 15/22 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 nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: ASPHD1 NM_181718.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.588
• Publications: 0 publications found

Genes affected

ASPHD1 (HGNC:27380): (aspartate beta-hydroxylase domain containing 1) Predicted to enable dioxygenase activity. Predicted to be involved in peptidyl-amino acid modification. Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.063189685).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_181718.4. 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
	ASPHD1	NM_181718.4	MANE Select	c.612C>G	p.Asp204Glu	missense	Exon 1 of 3	NP_859069.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ASPHD1	ENST00000308748.10	TSL:1 MANE Select	c.612C>G	p.Asp204Glu	missense	Exon 1 of 3	ENSP00000311447.5	Q5U4P2
	ASPHD1	ENST00000566693.1	TSL:1	n.612C>G		non_coding_transcript_exon	Exon 1 of 5	ENSP00000456801.1	Q5U4P2
	ASPHD1	ENST00000867089.1		c.612C>G	p.Asp204Glu	missense	Exon 1 of 2	ENSP00000537148.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Benign	-0.31	T
BayesDel_noAF	Benign	-0.68
CADD	Benign	11
DANN	Benign	0.97
DEOGEN2	Benign	0.0029	T
Eigen	Benign	-1.0
Eigen_PC	Benign	-0.90
FATHMM_MKL	Benign	0.49	N
M_CAP	Benign	0.0072	T
MetaRNN	Benign	0.063	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.14	N
PhyloP100		-0.59
PrimateAI	Uncertain	0.65	T
PROVEAN	Benign	-0.080	N
REVEL	Benign	0.050
Sift	Benign	0.27	T
Sift4G	Benign	0.63	T
Varity_R		0.054
gMVP		0.38

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr16-29912904;