chr7-35670232-C-G

Position:

• chr7-35670232-C-G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_022373.5(HERPUD2):​c.322G>C​(p.Ala108Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/21 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. A108G) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.0 (0 hom., cov: 27)
  • Failed GnomAD Quality Control
• Consequence: HERPUD2 NM_022373.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.963

Genes affected

HERPUD2 (HGNC:21915): (HERPUD family member 2) Predicted to be involved in endoplasmic reticulum unfolded protein response. Predicted to act upstream of or within spermatogenesis. Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.23921287).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
HERPUD2	NM_022373.5	c.322G>C	p.Ala108Pro	missense_variant	4/9	ENST00000311350.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HERPUD2	ENST00000311350.8	c.322G>C	p.Ala108Pro	missense_variant	4/9	1	NM_022373.5	P1

Frequencies

GnomAD3 genomes AF: 0.00 AC: 0 AN: 149006 Hom.: 0 Cov.: 27 FAILED QC

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome Cov.: 25

GnomAD4 genome Data not reliable, filtered out with message: AC0;AS_VQSR AF: 0.00 AC: 0 AN: 149006 Hom.: 0 Cov.: 27 AF XY: 0.00 AC XY: 0 AN XY: 72424

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00

Gnomad4 OTH AF: 0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.067
BayesDel_addAF	Benign	-0.19	T
BayesDel_noAF	Benign	-0.51
CADD	Benign	20
DANN	Uncertain	0.99
DEOGEN2	Benign	0.0030	T;T;.
Eigen	Benign	-0.10
Eigen_PC	Benign	-0.041
FATHMM_MKL	Uncertain	0.83	D
LIST_S2	Benign	0.73	.;T;T
M_CAP	Benign	0.014	T
MetaRNN	Benign	0.24	T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.7	L;L;.
MutationTaster	Benign	0.097	P;P
PrimateAI	Benign	0.38	T
PROVEAN	Benign	-0.78	N;N;N
REVEL	Benign	0.046
Sift	Benign	0.086	T;T;T
Sift4G	Benign	0.21	T;T;.
Polyphen		0.93	P;P;.
Vest4		0.13
MutPred		0.17		Gain of glycosylation at A108 (P = 0.0199);Gain of glycosylation at A108 (P = 0.0199);.;
MVP		0.34
MPC		0.37
ClinPred		0.42	T
GERP RS		2.2
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.087
gMVP		0.28

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

LitVar

Other links and lift over

dbSNP: rs3779234; hg19: chr7-35709842;