16-29901716-T-G

Position:

• chr16-29901716-T-G

Variant summary

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

The NM_181718.4(ASPHD1):​c.745T>G​(p.Cys249Gly) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: ASPHD1 NM_181718.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.69

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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ASPHD1	NM_181718.4	c.745T>G	p.Cys249Gly	missense_variant	1/3	ENST00000308748.10	NP_859069.2
ASPHD1	XM_017023107.2	c.292T>G	p.Cys98Gly	missense_variant	2/4		XP_016878596.1
ASPHD1	XR_007064864.1	n.1229T>G		non_coding_transcript_exon_variant	1/4
ASPHD1	XR_007064865.1	n.1229T>G		non_coding_transcript_exon_variant	1/5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ASPHD1	ENST00000308748.10	c.745T>G	p.Cys249Gly	missense_variant	1/3	1	NM_181718.4	ENSP00000311447.5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 32

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

Jun 06, 2023

The c.745T>G (p.C249G) alteration is located in exon 1 (coding exon 1) of the ASPHD1 gene. This alteration results from a T to G substitution at nucleotide position 745, causing the cysteine (C) at amino acid position 249 to be replaced by a glycine (G). 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	0.18
BayesDel_addAF	Uncertain	0.050	T
BayesDel_noAF	Benign	-0.17
CADD	Uncertain	23
DANN	Benign	0.95
DEOGEN2	Benign	0.064	T
Eigen	Uncertain	0.37
Eigen_PC	Uncertain	0.45
FATHMM_MKL	Uncertain	0.82	D
M_CAP	Benign	0.014	T
MetaRNN	Uncertain	0.43	T
MetaSVM	Benign	-0.94	T
MutationAssessor	Benign	0.34	N
PrimateAI	Uncertain	0.59	T
PROVEAN	Benign	2.4	N
REVEL	Benign	0.21
Sift	Benign	0.40	T
Sift4G	Benign	0.78	T
Polyphen		0.95	P
Vest4		0.47
MutPred		0.61		Gain of relative solvent accessibility (P = 0.0289);
MVP		0.74
MPC		1.5
ClinPred		0.59	D
GERP RS		5.7
Varity_R		0.24
gMVP		0.90

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr16-29913037;