rs142323760

Variant names:

• chr15-35410884-T-A
• NM_080650.4:c.518A>T

Your query was ambiguous. Multiple possible variants found:

• chr15-35410884-T-A
• chr15-35410884-T-C
• chr15-35410884-T-G

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_080650.4(DPH6):​c.518A>T​(p.Asp173Val) variant causes a missense change. The variant allele was found at a frequency of 0.000000688 in 1,453,280 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. D173A) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: DPH6 NM_080650.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.32

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 Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.36087322).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DPH6	NM_080650.4	c.518A>T	p.Asp173Val	missense_variant	Exon 6 of 9	ENST00000256538.9	NP_542381.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DPH6	ENST00000256538.9	c.518A>T	p.Asp173Val	missense_variant	Exon 6 of 9	1	NM_080650.4	ENSP00000256538.4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.88e-7 AC: 1 AN: 1453280 Hom.: 0 Cov.: 30 AF XY: 0.00000138 AC XY: 1 AN XY: 723010

Gnomad4 AFR exome AF: 0.00

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: 0.00

Gnomad4 OTH exome AF: 0.0000167

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.082
BayesDel_addAF	Benign	-0.027	T
BayesDel_noAF	Benign	-0.28
CADD	Uncertain	25
DANN	Benign	0.97
DEOGEN2	Benign	0.040	T;T;T
Eigen	Benign	0.094
Eigen_PC	Uncertain	0.23
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.97	D;D;D
M_CAP	Benign	0.015	T
MetaRNN	Benign	0.36	T;T;T
MetaSVM	Benign	-0.93	T
MutationAssessor	Benign	1.3	L;.;.
PrimateAI	Benign	0.43	T
PROVEAN	Pathogenic	-4.4	D;D;D
REVEL	Benign	0.15
Sift	Benign	0.088	T;T;T
Sift4G	Benign	0.085	T;D;.
Polyphen		0.0020	B;.;.
Vest4		0.53
MutPred		0.59		Loss of disorder (P = 0.0146);.;.;
MVP		0.45
MPC		0.26
ClinPred		0.98	D
GERP RS		5.3
Varity_R		0.45
gMVP		0.78

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: chr15-35703085;