6-44285654-C-T

Variant names:

• chr6-44285654-C-T
• rs9381307
• NM_182539.4:c.846+310G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_182539.4(DRC5):​c.846+310G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.157 in 152,150 control chromosomes in the GnomAD database, including 2,176 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.16 (2176 hom., cov: 32)
• Consequence: DRC5 NM_182539.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0820
• Publications: 3 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.78).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.39 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DRC5	NM_182539.4	c.846+310G>A		intron_variant	Intron 3 of 4	ENST00000371505.5	NP_872345.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TCTE1	ENST00000371505.5	c.846+310G>A		intron_variant	Intron 3 of 4	1	NM_182539.4	ENSP00000360560.4
ENSG00000272442	ENST00000505802.1	n.312+12148C>T		intron_variant	Intron 1 of 9	2		ENSP00000424257.1
TMEM151B	ENST00000438774.2	c.576+12148C>T		intron_variant	Intron 2 of 2	3		ENSP00000409337.2
TCTE1	ENST00000371504.1	c.387+310G>A		intron_variant	Intron 1 of 1	3		ENSP00000360559.1

Frequencies

GnomAD3 genomes AF: 0.157 AC: 23849 AN: 152030 Hom.: 2173 Cov.: 32

Gnomad AFR AF: 0.106

Gnomad AMI AF: 0.152

Gnomad AMR AF: 0.131

Gnomad ASJ AF: 0.154

Gnomad EAS AF: 0.404

Gnomad SAS AF: 0.263

Gnomad FIN AF: 0.219

Gnomad MID AF: 0.136

Gnomad NFE AF: 0.158

Gnomad OTH AF: 0.155

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.157 AC: 23866 AN: 152150 Hom.: 2176 Cov.: 32 AF XY: 0.162 AC XY: 12031 AN XY: 74362

African (AFR) AF: 0.106 AC: 4408 AN: 41512

American (AMR) AF: 0.131 AC: 1997 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.154 AC: 533 AN: 3472

East Asian (EAS) AF: 0.405 AC: 2091 AN: 5168

South Asian (SAS) AF: 0.264 AC: 1272 AN: 4822

European-Finnish (FIN) AF: 0.219 AC: 2318 AN: 10568

Middle Eastern (MID) AF: 0.122 AC: 36 AN: 294

European-Non Finnish (NFE) AF: 0.158 AC: 10740 AN: 68002

Other (OTH) AF: 0.158 AC: 333 AN: 2112

Alfa AF: 0.113 Hom.: 299

Bravo AF: 0.149

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	6.8
DANN	Benign	0.71
PhyloP100		0.082
Mutation Taster		=100/0	polymorphism (auto)

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: rs9381307; hg19: chr6-44253391;