3-197891488-C-A

Variant names:

• chr3-197891488-C-A
• NM_032263.5:c.1155G>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP6_Moderate

The NM_032263.5(DRC9):​c.1155G>T​(p.Lys385Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: DRC9 NM_032263.5 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.968
• 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]

ACMG classification

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

• PM2: Very rare variant in population databases, with high coverage
• BP6: Variant 3-197891488-C-A is Benign according to our data. Variant chr3-197891488-C-A is described in ClinVar as Likely_benign. ClinVar VariationId is 3286365.Status of the report is criteria_provided_single_submitter, 1 stars.

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.1155G>T	p.Lys385Asn	missense	Exon 11 of 12	NP_115639.1	Q9H095-1
	DRC9	NM_001134435.3		c.1155G>T	p.Lys385Asn	missense	Exon 10 of 11	NP_001127907.1	Q9H095-1
	DRC9	NM_001323027.2		c.1155G>T	p.Lys385Asn	missense	Exon 10 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.1155G>T	p.Lys385Asn	missense	Exon 11 of 12	ENSP00000265239.6	Q9H095-1
	IQCG	ENST00000960928.1		c.1287G>T	p.Lys429Asn	missense	Exon 12 of 13	ENSP00000630987.1
	IQCG	ENST00000960931.1		c.1287G>T	p.Lys429Asn	missense	Exon 11 of 12	ENSP00000630990.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 27

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions as Germline

Significance: Likely benign

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	0.18
BayesDel_addAF	Benign	-0.22	T
BayesDel_noAF	Benign	-0.56
CADD	Benign	23
DANN	Uncertain	0.99
DEOGEN2	Benign	0.035	T
Eigen	Benign	-0.51
Eigen_PC	Benign	-0.36
FATHMM_MKL	Uncertain	0.85	D
LIST_S2	Benign	0.39	T
M_CAP	Benign	0.0061	T
MetaRNN	Benign	0.11	T
MetaSVM	Benign	-1.1	T
PhyloP100		0.97
PrimateAI	Benign	0.48	T
PROVEAN	Uncertain	-2.6	D
REVEL	Benign	0.013
Sift	Benign	0.17	T
Sift4G	Benign	0.18	T
Polyphen		0.011	B
Vest4		0.23
MutPred		0.35		Gain of glycosylation at S383 (P = 0.0021)
MVP		0.54
MPC		0.27
ClinPred		0.66	D
GERP RS		2.5
Varity_R		0.13
gMVP		0.38
Mutation Taster		=91/9	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.26		Details are displayed if max score is > 0.2
DS_DG_spliceai		0.25		Position offset: -3
DS_DL_spliceai		0.26		Position offset: -42

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

hg19: chr3-197618359;