16-29901714-G-C

Position:

• chr16-29901714-G-C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_181718.4(ASPHD1):​c.743G>C​(p.Gly248Ala) 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: ASPHD1 NM_181718.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.04

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]

ASPHD1 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.2530862).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ASPHD1	NM_181718.4	c.743G>C	p.Gly248Ala	missense_variant	1/3	ENST00000308748.10	NP_859069.2
ASPHD1	XM_017023107.2	c.290G>C	p.Gly97Ala	missense_variant	2/4		XP_016878596.1
ASPHD1	XR_007064864.1	n.1227G>C		non_coding_transcript_exon_variant	1/4
ASPHD1	XR_007064865.1	n.1227G>C		non_coding_transcript_exon_variant	1/5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ASPHD1	ENST00000308748.10	c.743G>C	p.Gly248Ala	missense_variant	1/3	1	NM_181718.4	ENSP00000311447.5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Oct 21, 2024

The c.743G>C (p.G248A) alteration is located in exon 1 (coding exon 1) of the ASPHD1 gene. This alteration results from a G to C substitution at nucleotide position 743, causing the glycine (G) at amino acid position 248 to be replaced by an alanine (A). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.28
BayesDel_addAF	Benign	-0.10	T
BayesDel_noAF	Benign	-0.38
CADD	Pathogenic	26
DANN	Uncertain	1.0
DEOGEN2	Benign	0.0082	T
Eigen	Uncertain	0.34
Eigen_PC	Uncertain	0.44
FATHMM_MKL	Uncertain	0.92	D
M_CAP	Benign	0.0086	T
MetaRNN	Benign	0.25	T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	0.0	N
PrimateAI	Uncertain	0.71	T
PROVEAN	Benign	-0.91	N
REVEL	Benign	0.094
Sift	Benign	0.048	D
Sift4G	Benign	0.20	T
Polyphen		0.84	P
Vest4		0.21
MutPred		0.62		Gain of glycosylation at P247 (P = 0.1351);
MVP		0.70
MPC		1.2
ClinPred		0.70	D
GERP RS		5.7
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.29
gMVP		0.63

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

Publications

LitVar

Other links and lift over

dbSNP: rs2068551703; hg19: chr16-29913035;