rs200034926

Variant names:

• chr7-35670301-C-A
• rs200034926
• NM_022373.5:c.253G>T

Your query was ambiguous. Multiple possible variants found:

• chr7-35670301-C-A
• chr7-35670301-C-G
• chr7-35670301-C-T

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_022373.5(HERPUD2):​c.253G>T​(p.Val85Leu) variant causes a missense change. The variant allele was found at a frequency of 0.000000713 in 1,402,912 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. V85I) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 7.1e-7 (0 hom.)
• Consequence: HERPUD2 NM_022373.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.41
• Publications: 0 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: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HERPUD2	NM_022373.5	MANE Select	c.253G>T	p.Val85Leu	missense	Exon 4 of 9	NP_071768.3
	HERPUD2	NM_001438072.1		c.253G>T	p.Val85Leu	missense	Exon 3 of 8	NP_001425001.1
	HERPUD2	NM_001438070.1		c.148-2713G>T		intron	N/A	NP_001424999.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HERPUD2	ENST00000311350.8	TSL:1 MANE Select	c.253G>T	p.Val85Leu	missense	Exon 4 of 9	ENSP00000310729.3	Q9BSE4
	HERPUD2	ENST00000396081.5	TSL:1	c.253G>T	p.Val85Leu	missense	Exon 3 of 8	ENSP00000379390.1	Q9BSE4
	HERPUD2	ENST00000894710.1		c.253G>T	p.Val85Leu	missense	Exon 4 of 9	ENSP00000564769.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 7.13e-7 AC: 1 AN: 1402912 Hom.: 0 Cov.: 26 AF XY: 0.00 AC XY: 0 AN XY: 698170

African (AFR) AF: 0.0000319 AC: 1 AN: 31364

American (AMR) AF: 0.00 AC: 0 AN: 41190

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25008

East Asian (EAS) AF: 0.00 AC: 0 AN: 38064

South Asian (SAS) AF: 0.00 AC: 0 AN: 78240

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 51800

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5612

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1073724

Other (OTH) AF: 0.00 AC: 0 AN: 57910

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.98
BayesDel_addAF	Pathogenic	0.29	D
BayesDel_noAF	Pathogenic	0.17
CADD	Pathogenic	28
DANN	Uncertain	1.0
DEOGEN2	Benign	0.12	T
Eigen	Uncertain	0.60
Eigen_PC	Uncertain	0.50
FATHMM_MKL	Uncertain	0.97	D
LIST_S2	Uncertain	0.96	D
M_CAP	Benign	0.042	D
MetaRNN	Uncertain	0.68	D
MetaSVM	Uncertain	-0.19	T
MutationAssessor	Pathogenic	3.4	M
PhyloP100		5.4
PrimateAI	Uncertain	0.70	T
PROVEAN	Uncertain	-2.6	D
REVEL	Uncertain	0.45
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0	D
Polyphen		0.98	D
Vest4		0.75
MutPred		0.61		Loss of sheet (P = 0.1158)
MVP		0.81
MPC		0.86
ClinPred		0.99	D
GERP RS		3.8
Varity_R		0.81
gMVP		0.64
Mutation Taster		=52/48	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.060		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: rs200034926; hg19: chr7-35709911;