rs200034926

Variant names:

• chr7-35670301-C-A
• 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. Variant got 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

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 2 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HERPUD2	NM_022373.5	c.253G>T	p.Val85Leu	missense_variant	Exon 4 of 9	ENST00000311350.8	NP_071768.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HERPUD2	ENST00000311350.8	c.253G>T	p.Val85Leu	missense_variant	Exon 4 of 9	1	NM_022373.5	ENSP00000310729.3

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

Gnomad4 AFR exome AF: 0.0000319

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

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;T;.
Eigen	Uncertain	0.60
Eigen_PC	Uncertain	0.50
FATHMM_MKL	Uncertain	0.97	D
LIST_S2	Uncertain	0.96	.;D;D
M_CAP	Benign	0.042	D
MetaRNN	Uncertain	0.68	D;D;D
MetaSVM	Uncertain	-0.19	T
MutationAssessor	Pathogenic	3.4	M;M;.
PrimateAI	Uncertain	0.70	T
PROVEAN	Uncertain	-2.6	D;D;N
REVEL	Uncertain	0.45
Sift	Pathogenic	0.0	D;D;T
Sift4G	Pathogenic	0.0	D;D;.
Polyphen		0.98	D;D;.
Vest4		0.75
MutPred		0.61		Loss of sheet (P = 0.1158);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

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr7-35709911;