7-35670232-C-T

Position:

• chr7-35670232-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_022373.5(HERPUD2):​c.322G>A​(p.Ala108Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.36 in 1,553,080 control chromosomes in the GnomAD database, including 104,106 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 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 nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

• Frequency:
  • Genomes: 𝑓 0.31 (7958 hom., cov: 27)
  • Exomes 𝑓: 0.37 (96148 hom.)
• 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 Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0026303232).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.38 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HERPUD2	NM_022373.5	c.322G>A	p.Ala108Thr	missense_variant	4/9	ENST00000311350.8	NP_071768.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HERPUD2	ENST00000311350.8	c.322G>A	p.Ala108Thr	missense_variant	4/9	1	NM_022373.5	ENSP00000310729.3

Frequencies

GnomAD3 genomes AF: 0.313 AC: 46545 AN: 148874 Hom.: 7958 Cov.: 27

Gnomad AFR AF: 0.171

Gnomad AMI AF: 0.601

Gnomad AMR AF: 0.326

Gnomad ASJ AF: 0.401

Gnomad EAS AF: 0.254

Gnomad SAS AF: 0.344

Gnomad FIN AF: 0.338

Gnomad MID AF: 0.338

Gnomad NFE AF: 0.384

Gnomad OTH AF: 0.345

GnomAD3 exomes AF: 0.340 AC: 80514 AN: 236682 Hom.: 14377 AF XY: 0.348 AC XY: 44739 AN XY: 128384

Gnomad AFR exome AF: 0.165

Gnomad AMR exome AF: 0.295

Gnomad ASJ exome AF: 0.407

Gnomad EAS exome AF: 0.262

Gnomad SAS exome AF: 0.348

Gnomad FIN exome AF: 0.332

Gnomad NFE exome AF: 0.381

Gnomad OTH exome AF: 0.369

GnomAD4 exome AF: 0.365 AC: 512623 AN: 1404088 Hom.: 96148 Cov.: 25 AF XY: 0.367 AC XY: 256465 AN XY: 699758

Gnomad4 AFR exome AF: 0.157

Gnomad4 AMR exome AF: 0.302

Gnomad4 ASJ exome AF: 0.403

Gnomad4 EAS exome AF: 0.255

Gnomad4 SAS exome AF: 0.349

Gnomad4 FIN exome AF: 0.331

Gnomad4 NFE exome AF: 0.379

Gnomad4 OTH exome AF: 0.364

GnomAD4 genome AF: 0.313 AC: 46561 AN: 148992 Hom.: 7958 Cov.: 27 AF XY: 0.310 AC XY: 22482 AN XY: 72478

Gnomad4 AFR AF: 0.171

Gnomad4 AMR AF: 0.325

Gnomad4 ASJ AF: 0.401

Gnomad4 EAS AF: 0.254

Gnomad4 SAS AF: 0.344

Gnomad4 FIN AF: 0.338

Gnomad4 NFE AF: 0.384

Gnomad4 OTH AF: 0.343

Alfa AF: 0.371 Hom.: 25209

Bravo AF: 0.305

TwinsUK AF: 0.390 AC: 1447

ALSPAC AF: 0.382 AC: 1474

ESP6500AA AF: 0.176 AC: 775

ESP6500EA AF: 0.386 AC: 3319

ExAC AF: 0.335 AC: 40690

Asia WGS AF: 0.316 AC: 1099 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.063
BayesDel_addAF	Benign	-0.69	T
BayesDel_noAF	Benign	-0.61
CADD	Benign	17
DANN	Uncertain	0.98
DEOGEN2	Benign	0.00017	T;T;.
Eigen	Benign	-0.51
Eigen_PC	Benign	-0.33
FATHMM_MKL	Benign	0.35	N
LIST_S2	Benign	0.76	.;T;T
MetaRNN	Benign	0.0026	T;T;T
MetaSVM	Benign	-0.91	T
MutationAssessor	Benign	0.090	N;N;.
PrimateAI	Benign	0.36	T
PROVEAN	Benign	-0.070	N;N;N
REVEL	Benign	0.013
Sift	Benign	0.30	T;T;T
Sift4G	Benign	0.53	T;T;.
Polyphen		0.010	B;B;.
Vest4		0.024
MPC		0.28
ClinPred		0.0057	T
GERP RS		2.2
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.026
gMVP		0.23

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; COSMIC: COSV60943904; COSMIC: COSV60943904;