16-29901773-T-C

Position:

• chr16-29901773-T-C

Variant summary

Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2 PP3_Strong

The NM_181718.4(ASPHD1):​c.802T>C​(p.Cys268Arg) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. 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: 7.43

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 Likely_pathogenic. Variant got 6 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.94

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ASPHD1	NM_181718.4	c.802T>C	p.Cys268Arg	missense_variant	1/3	ENST00000308748.10	NP_859069.2
ASPHD1	XM_017023107.2	c.349T>C	p.Cys117Arg	missense_variant	2/4		XP_016878596.1
ASPHD1	XR_007064864.1	n.1286T>C		non_coding_transcript_exon_variant	1/4
ASPHD1	XR_007064865.1	n.1286T>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.802T>C	p.Cys268Arg	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

Apr 28, 2022

The c.802T>C (p.C268R) alteration is located in exon 1 (coding exon 1) of the ASPHD1 gene. This alteration results from a T to C substitution at nucleotide position 802, causing the cysteine (C) at amino acid position 268 to be replaced by an arginine (R). 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	Pathogenic	0.99
BayesDel_addAF	Pathogenic	0.28	D
BayesDel_noAF	Pathogenic	0.16
CADD	Pathogenic	29
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.42	T
Eigen	Pathogenic	0.87
Eigen_PC	Pathogenic	0.83
FATHMM_MKL	Pathogenic	0.99	D
M_CAP	Uncertain	0.17	D
MetaRNN	Pathogenic	0.94	D
MetaSVM	Benign	-0.37	T
MutationAssessor	Pathogenic	3.1	M
PrimateAI	Pathogenic	0.94	D
PROVEAN	Pathogenic	-7.2	D
REVEL	Pathogenic	0.75
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0	D
Polyphen		1.0	D
Vest4		0.91
MutPred		0.82		Gain of MoRF binding (P = 0.0179);
MVP		0.87
MPC		2.1
ClinPred		1.0	D
GERP RS		5.8
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.97
gMVP		0.98

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: chr16-29913094;