rs34907758

Variant names:

• chr15-35538464-C-T
• rs34907758
• NM_080650.4:c.122G>A

Your query was ambiguous. Multiple possible variants found:

• chr15-35538464-C-T
• chr15-35538464-C-A
• chr15-35538464-C-G

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_080650.4(DPH6):​c.122G>A​(p.Gly41Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00452 in 1,512,570 control chromosomes in the GnomAD database, including 227 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.022 (115 hom., cov: 32)
  • Exomes 𝑓: 0.0026 (112 hom.)
• Consequence: DPH6 NM_080650.4 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.0130
• Publications: 4 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: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0016201138).
• BP6: Variant 15-35538464-C-T is Benign according to our data. Variant chr15-35538464-C-T is described in ClinVar as Benign. ClinVar VariationId is 776871.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0723 is higher than 0.05.

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.122G>A	p.Gly41Glu	missense	Exon 3 of 9	NP_542381.1	Q7L8W6-1
	DPH6	NM_001141972.2		c.122G>A	p.Gly41Glu	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.122G>A	p.Gly41Glu	missense	Exon 3 of 9	ENSP00000256538.4	Q7L8W6-1
	DPH6	ENST00000440392.3	TSL:1	c.122G>A	p.Gly41Glu	missense	Exon 3 of 4	ENSP00000406976.2	Q7L8W6-2
	DPH6	ENST00000896513.1		c.122G>A	p.Gly41Glu	missense	Exon 3 of 9	ENSP00000566572.1

Frequencies

GnomAD3 genomes AF: 0.0218 AC: 3313 AN: 151986 Hom.: 115 Cov.: 32

Gnomad AFR AF: 0.0743

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0106

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00104

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0285

Gnomad NFE AF: 0.000427

Gnomad OTH AF: 0.0173

GnomAD2 exomes AF: 0.00638 AC: 1459 AN: 228604 AF XY: 0.00485

Gnomad AFR exome AF: 0.0794

Gnomad AMR exome AF: 0.00549

Gnomad ASJ exome AF: 0.000112

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000503

Gnomad OTH exome AF: 0.00459

GnomAD4 exome AF: 0.00258 AC: 3511 AN: 1360466 Hom.: 112 Cov.: 30 AF XY: 0.00232 AC XY: 1547 AN XY: 667604

African (AFR) AF: 0.0780 AC: 2457 AN: 31508

American (AMR) AF: 0.00622 AC: 243 AN: 39038

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 23494

East Asian (EAS) AF: 0.00 AC: 0 AN: 37896

South Asian (SAS) AF: 0.000210 AC: 15 AN: 71314

European-Finnish (FIN) AF: 0.0000401 AC: 2 AN: 49890

Middle Eastern (MID) AF: 0.0110 AC: 59 AN: 5378

European-Non Finnish (NFE) AF: 0.000335 AC: 351 AN: 1046768

Other (OTH) AF: 0.00696 AC: 384 AN: 55180

GnomAD4 genome AF: 0.0219 AC: 3329 AN: 152104 Hom.: 115 Cov.: 32 AF XY: 0.0214 AC XY: 1591 AN XY: 74348

African (AFR) AF: 0.0744 AC: 3089 AN: 41494

American (AMR) AF: 0.0106 AC: 162 AN: 15258

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5176

South Asian (SAS) AF: 0.00104 AC: 5 AN: 4816

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10600

Middle Eastern (MID) AF: 0.0272 AC: 8 AN: 294

European-Non Finnish (NFE) AF: 0.000427 AC: 29 AN: 67976

Other (OTH) AF: 0.0171 AC: 36 AN: 2106

Alfa AF: 0.00942 Hom.: 48

Bravo AF: 0.0254

TwinsUK AF: 0.00 AC: 0

ALSPAC AF: 0.000519 AC: 2

ESP6500AA AF: 0.0706 AC: 311

ESP6500EA AF: 0.000582 AC: 5

ExAC AF: 0.00727 AC: 882

Asia WGS AF: 0.00549 AC: 19 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.73	T
BayesDel_noAF	Benign	-0.76
CADD	Benign	14
DANN	Benign	0.81
DEOGEN2	Benign	0.0020	T
Eigen	Benign	-1.1
Eigen_PC	Benign	-0.88
FATHMM_MKL	Benign	0.11	N
LIST_S2	Benign	0.45	T
MetaRNN	Benign	0.0016	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-0.15	N
PhyloP100		-0.013
PrimateAI	Benign	0.32	T
PROVEAN	Benign	-1.0	N
REVEL	Benign	0.044
Sift	Benign	0.25	T
Sift4G	Benign	0.62	T
Polyphen		0.0	B
Vest4		0.11
MVP		0.20
MPC		0.22
ClinPred		0.0015	T
GERP RS		2.9
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.033
gMVP		0.29
Mutation Taster		=96/4	polymorphism (auto)

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

dbSNP: rs34907758; hg19: chr15-35830665;