16-57702008-C-T

Variant names:

• chr16-57702008-C-T
• rs781473941
• NM_001289162.2:c.577C>T

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_001289162.2(DRC7):​c.577C>T​(p.Leu193Phe) variant causes a missense change. The variant allele was found at a frequency of 0.000000684 in 1,461,876 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic 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: DRC7 NM_001289162.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.56
• Publications: 1 publications found

Genes affected

DRC7 (HGNC:25289): (dynein regulatory complex subunit 7) Predicted to be involved in flagellated sperm motility. Located in cytoplasm. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Uncertain_significance. The variant received 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.897

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001289162.2. 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
	DRC7	NM_001289162.2	MANE Select	c.577C>T	p.Leu193Phe	missense	Exon 6 of 19	NP_001276091.1	Q8IY82-1
	DRC7	NM_032269.6		c.577C>T	p.Leu193Phe	missense	Exon 5 of 18	NP_115645.4
	DRC7	NM_001289163.2		c.504+1738C>T		intron	N/A	NP_001276092.1	Q8IY82-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DRC7	ENST00000360716.8	TSL:1 MANE Select	c.577C>T	p.Leu193Phe	missense	Exon 6 of 19	ENSP00000353942.3	Q8IY82-1
	DRC7	ENST00000394337.8	TSL:1	c.577C>T	p.Leu193Phe	missense	Exon 5 of 18	ENSP00000377869.4	Q8IY82-1
	DRC7	ENST00000871948.1		c.577C>T	p.Leu193Phe	missense	Exon 6 of 19	ENSP00000542007.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00000398 AC: 1 AN: 251470 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000289

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461876 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 727244

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.0000224 AC: 1 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: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53416

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1111998

Other (OTH) AF: 0.00 AC: 0 AN: 60396

GnomAD4 genome Cov.: 32

ExAC AF: 0.0000165 AC: 2

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	Pathogenic	0.73
BayesDel_addAF	Uncertain	0.089	D
BayesDel_noAF	Uncertain	-0.030
CADD	Pathogenic	28
DANN	Uncertain	1.0
DEOGEN2	Benign	0.39	T
Eigen	Uncertain	0.41
Eigen_PC	Uncertain	0.31
FATHMM_MKL	Uncertain	0.90	D
LIST_S2	Uncertain	0.91	D
M_CAP	Uncertain	0.16	D
MetaRNN	Pathogenic	0.90	D
MetaSVM	Benign	-0.91	T
PhyloP100		4.6
PrimateAI	Uncertain	0.62	T
PROVEAN	Uncertain	-3.3	D
REVEL	Uncertain	0.37
Sift	Uncertain	0.021	D
Sift4G	Uncertain	0.0080	D
Polyphen		1.0	D
Vest4		0.87
MutPred		0.81		Loss of helix (P = 0.1706)
MVP		0.27
MPC		0.73
ClinPred		0.95	D
GERP RS		4.1
Varity_R		0.17
gMVP		0.74
Mutation Taster		=67/33	polymorphism

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: rs781473941; hg19: chr16-57735920;