rs766114531

Variant names:

• chr15-35454771-T-A
• NM_080650.4:c.362A>T

Your query was ambiguous. Multiple possible variants found:

• chr15-35454771-T-A
• chr15-35454771-T-C

Variant summary

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

The NM_080650.4(DPH6):​c.362A>T​(p.Tyr121Phe) variant causes a missense change. The variant allele was found at a frequency of 0.00000137 in 1,457,482 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: DPH6 NM_080650.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 6.72

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

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, 0.945

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DPH6	NM_080650.4	c.362A>T	p.Tyr121Phe	missense_variant	Exon 4 of 9	ENST00000256538.9	NP_542381.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DPH6	ENST00000256538.9	c.362A>T	p.Tyr121Phe	missense_variant	Exon 4 of 9	1	NM_080650.4	ENSP00000256538.4
DPH6	ENST00000561411.1	c.218A>T	p.Tyr73Phe	missense_variant	Exon 3 of 6	4		ENSP00000453967.1
DPH6	ENST00000559784.5	n.323A>T		non_coding_transcript_exon_variant	Exon 3 of 5	3
DPH6	ENST00000558266.5	c.-11A>T		upstream_gene_variant		5		ENSP00000454015.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1457482 Hom.: 0 Cov.: 29 AF XY: 0.00000276 AC XY: 2 AN XY: 724712

Gnomad4 AFR exome AF: 0.0000300

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 9.01e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.43
BayesDel_addAF	Uncertain	0.019	T
BayesDel_noAF	Benign	-0.21
CADD	Pathogenic	27
DANN	Uncertain	0.99
DEOGEN2	Benign	0.23	T;T
Eigen	Pathogenic	0.81
Eigen_PC	Pathogenic	0.75
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Pathogenic	1.0	D;D
M_CAP	Benign	0.027	D
MetaRNN	Pathogenic	0.94	D;D
MetaSVM	Benign	-0.49	T
MutationAssessor	Uncertain	2.7	M;.
PrimateAI	Uncertain	0.60	T
PROVEAN	Uncertain	-4.0	D;D
REVEL	Uncertain	0.40
Sift	Pathogenic	0.0	D;D
Sift4G	Pathogenic	0.0	D;.
Polyphen		1.0	D;.
Vest4		0.71
MutPred		0.92		Loss of sheet (P = 0.1158);.;
MVP		0.74
MPC		0.58
ClinPred		1.0	D
GERP RS		4.9
Varity_R		0.87
gMVP		0.78

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr15-35746972;