chr16-29901336-G-T

Position:

• chr16-29901336-G-T

Variant summary

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

The NM_181718.4(ASPHD1):​c.365G>T​(p.Cys122Phe) 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. 14/21 in silico tools predict 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: 31)
• Consequence: ASPHD1 NM_181718.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.17

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=0.18362147).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ASPHD1	NM_181718.4	c.365G>T	p.Cys122Phe	missense_variant	1/3	ENST00000308748.10	NP_859069.2
ASPHD1	XM_017023107.2	c.128-216G>T		intron_variant			XP_016878596.1
ASPHD1	XR_007064864.1	n.849G>T		non_coding_transcript_exon_variant	1/4
ASPHD1	XR_007064865.1	n.849G>T		non_coding_transcript_exon_variant	1/5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ASPHD1	ENST00000308748.10	c.365G>T	p.Cys122Phe	missense_variant	1/3	1	NM_181718.4	ENSP00000311447.5

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 31

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

Aug 04, 2024

The c.365G>T (p.C122F) alteration is located in exon 1 (coding exon 1) of the ASPHD1 gene. This alteration results from a G to T substitution at nucleotide position 365, causing the cysteine (C) at amino acid position 122 to be replaced by a phenylalanine (F). 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	0.090
BayesDel_addAF	Benign	-0.078	T
BayesDel_noAF	Benign	-0.35
CADD	Benign	21
DANN	Benign	0.96
DEOGEN2	Benign	0.0019	T
Eigen	Benign	-0.19
Eigen_PC	Benign	-0.12
FATHMM_MKL	Benign	0.67	D
M_CAP	Benign	0.033	D
MetaRNN	Benign	0.18	T
MetaSVM	Benign	-0.97	T
MutationAssessor	Benign	1.9	M
PrimateAI	Uncertain	0.57	T
PROVEAN	Benign	0.040	N
REVEL	Benign	0.12
Sift	Uncertain	0.0010	D
Sift4G	Benign	0.22	T
Polyphen		0.14	B
Vest4		0.36
MutPred		0.49		Gain of sheet (P = 0.0477);
MVP		0.60
MPC		1.2
ClinPred		0.57	D
GERP RS		4.7
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.66
gMVP		0.68

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: chr16-29912657;