3-197889680-C-G

Variant names:

• chr3-197889680-C-G
• rs139605751
• NM_032263.5:c.1232G>C

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_032263.5(DRC9):​c.1232G>C​(p.Arg411Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,774 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 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. R411K) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: DRC9 NM_032263.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.16
• Publications: 3 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]

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.23905885).

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.1232G>C	p.Arg411Thr	missense	Exon 12 of 12	NP_115639.1	Q9H095-1
	DRC9	NM_001134435.3		c.1232G>C	p.Arg411Thr	missense	Exon 11 of 11	NP_001127907.1	Q9H095-1
	DRC9	NM_001323027.2		c.1232G>C	p.Arg411Thr	missense	Exon 11 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.1232G>C	p.Arg411Thr	missense	Exon 12 of 12	ENSP00000265239.6	Q9H095-1
	IQCG	ENST00000960928.1		c.1364G>C	p.Arg455Thr	missense	Exon 13 of 13	ENSP00000630987.1
	IQCG	ENST00000960931.1		c.1364G>C	p.Arg455Thr	missense	Exon 12 of 12	ENSP00000630990.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD2 exomes AF: 0.00000398 AC: 1 AN: 251466 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: 0.00000879

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461774 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 727192

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.00 AC: 0 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: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53410

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

European-Non Finnish (NFE) AF: 8.99e-7 AC: 1 AN: 1111906

Other (OTH) AF: 0.00 AC: 0 AN: 60392

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.29
BayesDel_addAF	Benign	-0.22	T
BayesDel_noAF	Benign	-0.56
CADD	Benign	13
DANN	Benign	0.93
DEOGEN2	Benign	0.12	T
Eigen	Benign	-1.0
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.070	N
LIST_S2	Benign	0.71	T
M_CAP	Benign	0.065	D
MetaRNN	Benign	0.24	T
MetaSVM	Benign	-0.62	T
PhyloP100		-1.2
PrimateAI	Benign	0.23	T
PROVEAN	Uncertain	-3.3	D
REVEL	Benign	0.19
Sift	Uncertain	0.013	D
Sift4G	Benign	0.13	T
Polyphen		0.86	P
Vest4		0.26
MutPred		0.54		Gain of glycosylation at T407 (P = 0.0557)
MVP		0.072
MPC		0.89
ClinPred		0.57	D
GERP RS		-10
Varity_R		0.71
gMVP		0.39
Mutation Taster		=91/9	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: rs139605751; hg19: chr3-197616551;