rs755918980

Variant names:

• chr3-197938575-T-C
• rs755918980
• NM_032263.5:c.488A>G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_032263.5(DRC9):​c.488A>G​(p.Glu163Gly) variant causes a missense change. The variant allele was found at a frequency of 0.0000359 in 1,613,536 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000020 (0 hom., cov: 33)
  • Exomes 𝑓: 0.000038 (0 hom.)
• Consequence: DRC9 NM_032263.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.20
• Publications: 0 publications found

Genes affected

DRC9 (HGNC:25251): (IQ motif containing G) Enables Hsp70 protein binding activity and calmodulin binding activity. Predicted to be involved in sperm axoneme assembly. Located in cytoplasm. [provided by Alliance of Genome Resources, Apr 2022]

ENSG00000309418 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (MetaRNN=0.17036995).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_032263.5. 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
	DRC9	NM_032263.5	MANE Select	c.488A>G	p.Glu163Gly	missense	Exon 5 of 12	NP_115639.1	Q9H095-1
	DRC9	NM_001134435.3		c.488A>G	p.Glu163Gly	missense	Exon 4 of 11	NP_001127907.1	Q9H095-1
	DRC9	NM_001323027.2		c.488A>G	p.Glu163Gly	missense	Exon 4 of 11	NP_001309956.1	Q9H095-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IQCG	ENST00000265239.11	TSL:1 MANE Select	c.488A>G	p.Glu163Gly	missense	Exon 5 of 12	ENSP00000265239.6	Q9H095-1
	IQCG	ENST00000960928.1		c.488A>G	p.Glu163Gly	missense	Exon 5 of 13	ENSP00000630987.1
	IQCG	ENST00000960931.1		c.488A>G	p.Glu163Gly	missense	Exon 4 of 12	ENSP00000630990.1

Frequencies

GnomAD3 genomes AF: 0.0000197 AC: 3 AN: 152226 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000196

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: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000179 AC: 45 AN: 251462 AF XY: 0.000118

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00130

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000376 AC: 55 AN: 1461310 Hom.: 0 Cov.: 30 AF XY: 0.0000261 AC XY: 19 AN XY: 727028

African (AFR) AF: 0.00 AC: 0 AN: 33460

American (AMR) AF: 0.00123 AC: 55 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86244

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53420

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1111494

Other (OTH) AF: 0.00 AC: 0 AN: 60364

GnomAD4 genome AF: 0.0000197 AC: 3 AN: 152226 Hom.: 0 Cov.: 33 AF XY: 0.0000269 AC XY: 2 AN XY: 74366

African (AFR) AF: 0.00 AC: 0 AN: 41460

American (AMR) AF: 0.000196 AC: 3 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5196

South Asian (SAS) AF: 0.00 AC: 0 AN: 4828

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10624

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68046

Other (OTH) AF: 0.00 AC: 0 AN: 2092

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.000113

ExAC AF: 0.000132 AC: 16

ClinVar

ClinVar submissions as Germline

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.22
BayesDel_addAF	Benign	-0.32	T
BayesDel_noAF	Benign	-0.27
CADD	Uncertain	24
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.083	T
Eigen	Uncertain	0.62
Eigen_PC	Uncertain	0.60
FATHMM_MKL	Uncertain	0.90	D
LIST_S2	Benign	0.73	T
M_CAP	Benign	0.031	D
MetaRNN	Benign	0.17	T
MetaSVM	Benign	-0.47	T
PhyloP100		4.2
PrimateAI	Uncertain	0.49	T
PROVEAN	Uncertain	-4.1	D
REVEL	Benign	0.24
Sift	Uncertain	0.017	D
Sift4G	Uncertain	0.012	D
Polyphen		0.99	D
Vest4		0.49
MVP		0.52
MPC		0.84
ClinPred		0.60	D
GERP RS		5.5
Varity_R		0.26
gMVP		0.25
Mutation Taster		=59/41	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.12		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: rs755918980; hg19: chr3-197665446;