16-29901583-C-T

Variant names:

• chr16-29901583-C-T
• rs770388990
• NM_181718.4:c.612C>T

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP7

The NM_181718.4(ASPHD1):​c.612C>T​(p.Asp204Asp) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000719 in 1,389,892 control chromosomes in the GnomAD database, with no homozygous occurrence. 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)
  • Exomes 𝑓: 7.2e-7 (0 hom.)
• Consequence: ASPHD1 NM_181718.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.588
• 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: Likely_benign. The variant received -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.59).
• BP7: Synonymous conserved (PhyloP=-0.588 with no splicing effect.

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.612C>T	p.Asp204Asp	synonymous	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.612C>T	p.Asp204Asp	synonymous	Exon 1 of 3	ENSP00000311447.5	Q5U4P2
	ASPHD1	ENST00000566693.1	TSL:1	n.612C>T		non_coding_transcript_exon	Exon 1 of 5	ENSP00000456801.1	Q5U4P2
	ASPHD1	ENST00000483405.5	TSL:3	c.-232C>T		5_prime_UTR_premature_start_codon_gain	Exon 2 of 4	ENSP00000459527.1	I3L2A5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 7.19e-7 AC: 1 AN: 1389892 Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0 AN XY: 687566

African (AFR) AF: 0.00 AC: 0 AN: 31118

American (AMR) AF: 0.00 AC: 0 AN: 33116

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 21696

East Asian (EAS) AF: 0.00 AC: 0 AN: 39174

South Asian (SAS) AF: 0.00 AC: 0 AN: 76638

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 40568

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5456

European-Non Finnish (NFE) AF: 9.22e-7 AC: 1 AN: 1084714

Other (OTH) AF: 0.00 AC: 0 AN: 57412

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.59
CADD	Benign	8.9
DANN	Benign	0.92
PhyloP100		-0.59
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7

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

Other links and lift over

dbSNP: rs770388990; hg19: chr16-29912904; COSMIC: COSV58097834; COSMIC: COSV58097834;