6-44282115-C-G

Variant names:

• chr6-44282115-C-G
• NM_182539.4:c.1291G>C
• DRC5 p.Gly431Arg

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2 PP3

The NM_182539.4(DRC5):​c.1291G>C​(p.Gly431Arg) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar.

• Frequency: Genomes: not found (cov: 33)
• Consequence: DRC5 NM_182539.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.62
• Publications: 0 publications found

Genes affected

DRC5 (HGNC:11693): (t-complex-associated-testis-expressed 1) Predicted to be involved in flagellated sperm motility. Predicted to be located in sperm flagellum. [provided by Alliance of Genome Resources, Apr 2022]

ENSG00000272442 (HGNC:):

TMEM151B (HGNC:21315): (transmembrane protein 151B) Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Uncertain_significance. The variant received 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.77

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_182539.4. 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
	DRC5	NM_182539.4	MANE Select	c.1291G>C	p.Gly431Arg	missense	Exon 4 of 5	NP_872345.2	Q5JU00

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TCTE1	ENST00000371505.5	TSL:1 MANE Select	c.1291G>C	p.Gly431Arg	missense	Exon 4 of 5	ENSP00000360560.4	Q5JU00
	ENSG00000272442	ENST00000505802.1	TSL:2	n.312+8609C>G		intron	N/A	ENSP00000424257.1	H0Y9J4
	TCTE1	ENST00000897136.1		c.1291G>C	p.Gly431Arg	missense	Exon 4 of 5	ENSP00000567195.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.75
BayesDel_addAF	Pathogenic	0.30	D
BayesDel_noAF	Pathogenic	0.19
CADD	Pathogenic	27
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.055	T
Eigen	Pathogenic	0.77
Eigen_PC	Pathogenic	0.72
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.88	D
M_CAP	Uncertain	0.11	D
MetaRNN	Pathogenic	0.77	D
MetaSVM	Uncertain	-0.23	T
PhyloP100		4.6
PrimateAI	Uncertain	0.75	T
PROVEAN	Pathogenic	-6.5	D
REVEL	Uncertain	0.48
Sift	Uncertain	0.0030	D
Sift4G	Uncertain	0.0060	D
Varity_R		0.74
gMVP		0.80
Mutation Taster		=23/77	disease causing

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr6-44249852;