rs164009

Variant names:

• chr17-76287588-A-G
• rs164009
• NM_001388453.1:c.3896+212T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001388453.1(QRICH2):​c.3896+212T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.525 in 151,850 control chromosomes in the GnomAD database, including 23,067 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.52 (23067 hom., cov: 30)
• Consequence: QRICH2 NM_001388453.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.701
• Publications: 29 publications found

Genes affected

QRICH2 (HGNC:25326): (glutamine rich 2) Involved in cell projection assembly; flagellated sperm motility; and negative regulation of ubiquitin-dependent protein catabolic process. Located in sperm flagellum. Implicated in spermatogenic failure 35. [provided by Alliance of Genome Resources, Apr 2022]

QRICH2 Gene-Disease associations (from GenCC):

• spermatogenic failure 35

  Inheritance: AR Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.771 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
QRICH2	NM_001388453.1	c.3896+212T>C		intron_variant	Intron 6 of 18	ENST00000680821.2	NP_001375382.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
QRICH2	ENST00000680821.2	c.3896+212T>C		intron_variant	Intron 6 of 18		NM_001388453.1	ENSP00000504874.1

Frequencies

GnomAD3 genomes AF: 0.525 AC: 79593 AN: 151732 Hom.: 23037 Cov.: 30

Gnomad AFR AF: 0.779

Gnomad AMI AF: 0.412

Gnomad AMR AF: 0.516

Gnomad ASJ AF: 0.531

Gnomad EAS AF: 0.667

Gnomad SAS AF: 0.539

Gnomad FIN AF: 0.335

Gnomad MID AF: 0.465

Gnomad NFE AF: 0.391

Gnomad OTH AF: 0.514

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.525 AC: 79669 AN: 151850 Hom.: 23067 Cov.: 30 AF XY: 0.523 AC XY: 38782 AN XY: 74204

African (AFR) AF: 0.779 AC: 32253 AN: 41428

American (AMR) AF: 0.515 AC: 7843 AN: 15242

Ashkenazi Jewish (ASJ) AF: 0.531 AC: 1843 AN: 3470

East Asian (EAS) AF: 0.667 AC: 3428 AN: 5140

South Asian (SAS) AF: 0.541 AC: 2605 AN: 4816

European-Finnish (FIN) AF: 0.335 AC: 3534 AN: 10556

Middle Eastern (MID) AF: 0.463 AC: 136 AN: 294

European-Non Finnish (NFE) AF: 0.391 AC: 26573 AN: 67890

Other (OTH) AF: 0.513 AC: 1082 AN: 2110

Alfa AF: 0.450 Hom.: 44547

Bravo AF: 0.551

Asia WGS AF: 0.597 AC: 2075 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.42
DANN	Benign	0.81
PhyloP100		-0.70
Mutation Taster		=100/0	polymorphism (auto)

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: rs164009; hg19: chr17-74283669;