NM_032263.5:c.779C>T

Variant names:

• chr3-197913990-G-A
• rs777094497
• NM_032263.5:c.779C>T

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_032263.5(DRC9):​c.779C>T​(p.Ala260Val) variant causes a missense change. The variant allele was found at a frequency of 0.000000684 in 1,461,802 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: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: DRC9 NM_032263.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.66
• 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: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.4039953).

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.779C>T	p.Ala260Val	missense	Exon 8 of 12	NP_115639.1	Q9H095-1
	DRC9	NM_001134435.3		c.779C>T	p.Ala260Val	missense	Exon 7 of 11	NP_001127907.1	Q9H095-1
	DRC9	NM_001323027.2		c.779C>T	p.Ala260Val	missense	Exon 7 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.779C>T	p.Ala260Val	missense	Exon 8 of 12	ENSP00000265239.6	Q9H095-1
	IQCG	ENST00000960928.1		c.779C>T	p.Ala260Val	missense	Exon 8 of 13	ENSP00000630987.1
	IQCG	ENST00000960931.1		c.779C>T	p.Ala260Val	missense	Exon 7 of 12	ENSP00000630990.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461802 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 727214

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: 86254

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: 8.99e-7 AC: 1 AN: 1111928

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

GnomAD4 genome Cov.: 32

EpiCase AF: 0.00

EpiControl AF: 0.0000593

ClinVar

ClinVar submissions

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	0.32
BayesDel_addAF	Uncertain	0.031	T
BayesDel_noAF	Benign	-0.19
CADD	Pathogenic	27
DANN	Uncertain	1.0
DEOGEN2	Benign	0.066	T
Eigen	Uncertain	0.59
Eigen_PC	Uncertain	0.61
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Benign	0.84	T
M_CAP	Benign	0.020	T
MetaRNN	Benign	0.40	T
MetaSVM	Benign	-0.72	T
PhyloP100		6.7
PrimateAI	Uncertain	0.55	T
PROVEAN	Uncertain	-3.1	D
REVEL	Benign	0.20
Sift	Benign	0.20	T
Sift4G	Benign	0.22	T
Polyphen		0.94	P
Vest4		0.48
MutPred		0.48		Gain of glycosylation at S262 (P = 0.0304)
MVP		0.72
MPC		0.75
ClinPred		0.98	D
GERP RS		5.8
Varity_R		0.33
gMVP		0.27
Mutation Taster		=69/31	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs777094497; hg19: chr3-197640861;