chr16-29901318-G-A

Variant names:

• chr16-29901318-G-A
• rs1041348374
• NM_181718.4:c.347G>A

Variant summary

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

The NM_181718.4(ASPHD1):​c.347G>A​(p.Arg116His) 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. 16/22 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 variant affecting the same amino acid position, but resulting in a different missense (i.e. R116L) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 31)
• Consequence: ASPHD1 NM_181718.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.625
• 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: 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=0.08405578).

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.347G>A	p.Arg116His	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.347G>A	p.Arg116His	missense	Exon 1 of 3	ENSP00000311447.5	Q5U4P2
	ASPHD1	ENST00000566693.1	TSL:1	n.347G>A		non_coding_transcript_exon	Exon 1 of 5	ENSP00000456801.1	Q5U4P2
	ASPHD1	ENST00000867089.1		c.347G>A	p.Arg116His	missense	Exon 1 of 2	ENSP00000537148.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 31

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	0.089
BayesDel_addAF	Benign	-0.22	T
BayesDel_noAF	Benign	-0.55
CADD	Benign	18
DANN	Benign	0.97
DEOGEN2	Benign	0.0022	T
Eigen	Benign	-0.61
Eigen_PC	Benign	-0.54
FATHMM_MKL	Benign	0.083	N
M_CAP	Benign	0.016	T
MetaRNN	Benign	0.084	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.69	N
PhyloP100		0.63
PrimateAI	Benign	0.48	T
PROVEAN	Benign	0.29	N
REVEL	Benign	0.043
Sift	Benign	0.10	T
Sift4G	Benign	0.087	T
Polyphen		0.31	B
Vest4		0.082
MutPred		0.23		Loss of methylation at R116 (P = 0.0125)
MVP		0.51
MPC		0.76
ClinPred		0.12	T
GERP RS		4.0
PromoterAI		-0.0095	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.11
gMVP		0.31

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs1041348374; hg19: chr16-29912639;