rs3779234

Variant names:

• chr7-35670232-C-A
• rs3779234
• NM_022373.5:c.322G>T

Your query was ambiguous. Multiple possible variants found:

• chr7-35670232-C-A
• chr7-35670232-C-G
• chr7-35670232-C-T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_022373.5(HERPUD2):​c.322G>T​(p.Ala108Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000128 in 1,558,926 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 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 0.0000067 (0 hom., cov: 27)
  • Exomes 𝑓: 7.1e-7 (0 hom.)
• Consequence: HERPUD2 NM_022373.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.963
• Publications: 40 publications found

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

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.061363727).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_022373.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HERPUD2	NM_022373.5	MANE Select	c.322G>T	p.Ala108Ser	missense	Exon 4 of 9	NP_071768.3
	HERPUD2	NM_001438072.1		c.322G>T	p.Ala108Ser	missense	Exon 3 of 8	NP_001425001.1
	HERPUD2	NM_001438070.1		c.148-2644G>T		intron	N/A	NP_001424999.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HERPUD2	ENST00000311350.8	TSL:1 MANE Select	c.322G>T	p.Ala108Ser	missense	Exon 4 of 9	ENSP00000310729.3
	HERPUD2	ENST00000396081.5	TSL:1	c.322G>T	p.Ala108Ser	missense	Exon 3 of 8	ENSP00000379390.1
	HERPUD2	ENST00000413517.1	TSL:5	c.244G>T	p.Ala82Ser	missense	Exon 2 of 5	ENSP00000391015.1

Frequencies

GnomAD3 genomes AF: 0.00000671 AC: 1 AN: 149006 Hom.: 0 Cov.: 27

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: 0.0000148

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.00000423 AC: 1 AN: 236682 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000919

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 7.09e-7 AC: 1 AN: 1409920 Hom.: 0 Cov.: 25 AF XY: 0.00 AC XY: 0 AN XY: 702394

African (AFR) AF: 0.00 AC: 0 AN: 31714

American (AMR) AF: 0.00 AC: 0 AN: 42010

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25250

East Asian (EAS) AF: 0.00 AC: 0 AN: 38280

South Asian (SAS) AF: 0.00 AC: 0 AN: 80382

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52294

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5648

European-Non Finnish (NFE) AF: 9.29e-7 AC: 1 AN: 1076072

Other (OTH) AF: 0.00 AC: 0 AN: 58270

GnomAD4 genome AF: 0.00000671 AC: 1 AN: 149006 Hom.: 0 Cov.: 27 AF XY: 0.00 AC XY: 0 AN XY: 72424

African (AFR) AF: 0.00 AC: 0 AN: 40224

American (AMR) AF: 0.00 AC: 0 AN: 14780

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3450

East Asian (EAS) AF: 0.00 AC: 0 AN: 5126

South Asian (SAS) AF: 0.00 AC: 0 AN: 4664

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10134

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 314

European-Non Finnish (NFE) AF: 0.0000148 AC: 1 AN: 67374

Other (OTH) AF: 0.00 AC: 0 AN: 2036

Alfa AF: 0.00 Hom.: 33030

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.071
BayesDel_addAF	Benign	-0.21	T
BayesDel_noAF	Benign	-0.54
CADD	Benign	13
DANN	Benign	0.96
DEOGEN2	Benign	0.00044	T
Eigen	Benign	-0.54
Eigen_PC	Benign	-0.36
FATHMM_MKL	Uncertain	0.86	D
LIST_S2	Benign	0.79	T
M_CAP	Benign	0.0091	T
MetaRNN	Benign	0.061	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.4	L
PhyloP100		0.96
PrimateAI	Benign	0.34	T
PROVEAN	Benign	-0.41	N
REVEL	Benign	0.0090
Sift	Benign	0.18	T
Sift4G	Benign	0.46	T
Polyphen		0.068	B
Vest4		0.20
MutPred		0.21		Gain of phosphorylation at A108 (P = 0.0017)
MVP		0.39
MPC		0.27
ClinPred		0.069	T
GERP RS		2.2
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.033
gMVP		0.22
Mutation Taster		=94/6	polymorphism

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

Other links and lift over

dbSNP: rs3779234; hg19: chr7-35709842;