chr3-197912700-T-G

Variant names:

• chr3-197912700-T-G
• rs36078246
• NM_032263.5:c.938A>C

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

The NM_032263.5(DRC9):​c.938A>C​(p.Glu313Ala) variant causes a missense change. The variant allele was found at a frequency of 0.00056 in 1,613,798 control chromosomes in the GnomAD database, including 4 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0032 (2 hom., cov: 33)
  • Exomes 𝑓: 0.00028 (2 hom.)
• Consequence: DRC9 NM_032263.5 missense
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 4.82
• Publications: 2 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: Benign. The variant received -10 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.014394671).
• BP6: Variant 3-197912700-T-G is Benign according to our data. Variant chr3-197912700-T-G is described in ClinVar as Benign. ClinVar VariationId is 721584.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Homozygotes in GnomAd4 at 2 AR gene

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.938A>C	p.Glu313Ala	missense	Exon 9 of 12	NP_115639.1	Q9H095-1
	DRC9	NM_001134435.3		c.938A>C	p.Glu313Ala	missense	Exon 8 of 11	NP_001127907.1	Q9H095-1
	DRC9	NM_001323027.2		c.938A>C	p.Glu313Ala	missense	Exon 8 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.938A>C	p.Glu313Ala	missense	Exon 9 of 12	ENSP00000265239.6	Q9H095-1
	IQCG	ENST00000960928.1		c.938A>C	p.Glu313Ala	missense	Exon 9 of 13	ENSP00000630987.1
	IQCG	ENST00000960931.1		c.938A>C	p.Glu313Ala	missense	Exon 8 of 12	ENSP00000630990.1

Frequencies

GnomAD3 genomes AF: 0.00318 AC: 483 AN: 152070 Hom.: 2 Cov.: 33

Gnomad AFR AF: 0.0107

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00223

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: 0.00191

GnomAD2 exomes AF: 0.000803 AC: 202 AN: 251424 AF XY: 0.000626

Gnomad AFR exome AF: 0.0106

Gnomad AMR exome AF: 0.000665

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: 0.000489

GnomAD4 exome AF: 0.000282 AC: 412 AN: 1461610 Hom.: 2 Cov.: 30 AF XY: 0.000245 AC XY: 178 AN XY: 727118

African (AFR) AF: 0.00995 AC: 333 AN: 33476

American (AMR) AF: 0.000716 AC: 32 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26130

East Asian (EAS) AF: 0.00 AC: 0 AN: 39694

South Asian (SAS) AF: 0.0000232 AC: 2 AN: 86254

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53256

Middle Eastern (MID) AF: 0.000694 AC: 4 AN: 5766

European-Non Finnish (NFE) AF: 0.00000270 AC: 3 AN: 1111926

Other (OTH) AF: 0.000629 AC: 38 AN: 60386

GnomAD4 genome AF: 0.00323 AC: 491 AN: 152188 Hom.: 2 Cov.: 33 AF XY: 0.00325 AC XY: 242 AN XY: 74400

African (AFR) AF: 0.0109 AC: 453 AN: 41558

American (AMR) AF: 0.00222 AC: 34 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5186

South Asian (SAS) AF: 0.00 AC: 0 AN: 4826

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10524

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68008

Other (OTH) AF: 0.00189 AC: 4 AN: 2114

Alfa AF: 0.00132 Hom.: 3

Bravo AF: 0.00377

TwinsUK AF: 0.00 AC: 0

ALSPAC AF: 0.000259 AC: 1

ESP6500AA AF: 0.0118 AC: 52

ESP6500EA AF: 0.00 AC: 0

ExAC AF: 0.000955 AC: 116

Asia WGS AF: 0.000289 AC: 1 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, single submitter

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.37
BayesDel_addAF	Benign	-0.38	T
BayesDel_noAF	Benign	-0.31
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.23	T
Eigen	Uncertain	0.64
Eigen_PC	Uncertain	0.56
FATHMM_MKL	Uncertain	0.92	D
LIST_S2	Benign	0.81	T
MetaRNN	Benign	0.014	T
MetaSVM	Benign	-0.31	T
PhyloP100		4.8
PrimateAI	Uncertain	0.59	T
PROVEAN	Pathogenic	-5.5	D
REVEL	Benign	0.22
Sift	Uncertain	0.0040	D
Sift4G	Benign	0.067	T
Polyphen		1.0	D
Vest4		0.85
MVP		0.76
MPC		0.86
ClinPred		0.041	T
GERP RS		5.6
Varity_R		0.58
gMVP		0.60
Mutation Taster		=98/2	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
Splicevardb		2.0
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: rs36078246; hg19: chr3-197639571;