NM_080650.4:c.290A>G

Variant names:

• chr15-35538296-T-C
• NM_080650.4:c.290A>G

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_080650.4(DPH6):​c.290A>G​(p.Tyr97Cys) variant causes a missense change. The variant allele was found at a frequency of 0.00000351 in 1,424,416 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000035 (0 hom.)
• Consequence: DPH6 NM_080650.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.01
• Publications: 0 publications found

Genes affected

DPH6 (HGNC:30543): (diphthamine biosynthesis 6) Enables diphthine-ammonia ligase activity. Predicted to be involved in peptidyl-diphthamide biosynthetic process from peptidyl-histidine. Located in nucleolus and nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_080650.4. 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
	DPH6	NM_080650.4	MANE Select	c.290A>G	p.Tyr97Cys	missense	Exon 3 of 9	NP_542381.1	Q7L8W6-1
	DPH6	NM_001141972.2		c.290A>G	p.Tyr97Cys	missense	Exon 3 of 4	NP_001135444.1	Q7L8W6-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DPH6	ENST00000256538.9	TSL:1 MANE Select	c.290A>G	p.Tyr97Cys	missense	Exon 3 of 9	ENSP00000256538.4	Q7L8W6-1
	DPH6	ENST00000440392.3	TSL:1	c.290A>G	p.Tyr97Cys	missense	Exon 3 of 4	ENSP00000406976.2	Q7L8W6-2
	DPH6	ENST00000896513.1		c.290A>G	p.Tyr97Cys	missense	Exon 3 of 9	ENSP00000566572.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000351 AC: 5 AN: 1424416 Hom.: 0 Cov.: 30 AF XY: 0.00000426 AC XY: 3 AN XY: 703858

African (AFR) AF: 0.00 AC: 0 AN: 32994

American (AMR) AF: 0.00 AC: 0 AN: 44304

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25370

East Asian (EAS) AF: 0.00 AC: 0 AN: 38976

South Asian (SAS) AF: 0.00 AC: 0 AN: 82450

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52430

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5622

European-Non Finnish (NFE) AF: 0.00000461 AC: 5 AN: 1083786

Other (OTH) AF: 0.00 AC: 0 AN: 58484

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.17
BayesDel_addAF	Uncertain	0.069	T
BayesDel_noAF	Benign	-0.14
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.13	T
Eigen	Uncertain	0.56
Eigen_PC	Uncertain	0.59
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Pathogenic	0.99	D
M_CAP	Benign	0.033	D
MetaRNN	Uncertain	0.69	D
MetaSVM	Benign	-0.34	T
MutationAssessor	Uncertain	2.9	M
PhyloP100		5.0
PrimateAI	Uncertain	0.57	T
PROVEAN	Pathogenic	-7.3	D
REVEL	Benign	0.26
Sift	Uncertain	0.012	D
Sift4G	Uncertain	0.016	D
Polyphen		0.058	B
Vest4		0.68
MutPred		0.49		Loss of phosphorylation at Y97 (P = 0.0277)
MVP		0.63
MPC		0.56
ClinPred		1.0	D
GERP RS		4.9
Varity_R		0.91
gMVP		0.79

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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

hg19: chr15-35830497;